Semaglutide Weight Management and Cardiovascular Risk Reduction

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#1novo nordisk Novo Nordisk -a focused healthcare company Novo Nordisk investor event in connection with ADA San Diego, 25 June 2023#2Forward-looking statements Novo Nordisk's reports filed with or furnished to the US Securities and Exchange Commission (SEC), including the statutory Annual Report 2022 and Form 20-F, which both were filed with the SEC in February 2023 in continuation of the publication of this Annual Report 2022, this presentation, and written information released, or oral statements made, to the public in the future by or on behalf of Novo Nordisk, may contain forward-looking statements. Words such as 'believe', 'expect, 'may', 'will', 'plan', 'strategy', 'prospect', 'foresee', 'estimate', 'project', 'anticipate', 'can', 'intend', 'target' and other words and terms of similar meaning in connection with any discussion of future operating or financial performance identify forward-looking statements. Examples of such forward-looking statements include, but are not limited to: • Statements of targets, plans, objectives or goals for future operations, including those related to Novo Nordisk's products, product research, product development, product introductions and product approvals as well as cooperation in relation thereto, Statements containing projections of or targets for revenues, costs, income (or loss), earnings per share, capital expenditures, dividends, capital structure, net financials and other financial measures, • • Statements regarding future economic performance, future actions and outcome of contingencies such as legal proceedings, and Statements regarding the assumptions underlying or relating to such statements. These statements are based on current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific. Novo Nordisk cautions that a number of important factors, including those described in this presentation, could cause actual results to differ materially from those contemplated in any forward-looking statements. Factors that may affect future results include, but are not limited to, global as well as local political and economic conditions, such as interest rate and currency exchange rate fluctuations, delay or failure of projects related to research and/or development, unplanned loss of patents, interruptions of supplies and production, including as a result of interruptions or delays affecting supply chains on which Novo Nordisk relies, shortages of supplies, including energy supplies, product recalls, unexpected contract breaches or terminations, government- mandated or market-driven price decreases for Novo Nordisk's products, introduction of competing products, reliance on information technology including the risk of cybersecurity breeches, Novo Nordisk's ability to successfully market current and new products, exposure to product liability and legal proceedings and investigations, changes in governmental laws and related interpretation thereof, including on reimbursement, intellectual property protection and regulatory controls on testing, approval, manufacturing and marketing, perceived or actual failure to adhere to ethical marketing practices, investments in and divestitures of domestic and foreign companies, unexpected growth in costs and expenses, strikes and other labour market dispute, failure to recruit and retain the right employees, failure to maintain a culture of compliance, and epidemics, pandemics or other public health crises, and the effects of domestic or international crises, civil unrest, war or other conflict. For an overview of some, but not all, of the risks that could adversely affect Novo Nordisk's results or the accuracy of forward-looking statements in this Annual Report 2022, reference is made to the overview of risk factors in 'Risk management' of this Annual Report 2022. Unless required by law, Novo Nordisk is under no duty and undertakes no obligation to update or revise any forward-looking statement after the distribution of this Annual Report 2022, whether as a result of new information, future events, or otherwise. Important drug information VictozaⓇ and OzempicⓇ are approved for the management of type 2 diabetes only SaxendaⓇ and WegovyⓇ are approved for the treatment of obesity only#3Commercial execution Purpose and sustainability (ESG) Strategic Aspirations 2025 | Highlights first three months 2023 Progress towards zero environmental impact Carbon emissions decreased by 21% vs Q1 20191 Adding value to society Medical treatment provided to 37.2 million people living with diabetes Reaching more than 42,000 children in Changing Diabetes in Children programme Being recognised as a sustainable employer Share of women in senior leadership positions has increased to 39% from 37% end of March 2022 ピ Diabetes value market share increased by 1.7%-points to 32.2%2 Obesity care sales of DKK 7.8 billion (+124% at CER) Rare disease sales of DKK 4.6 billion (-16% at CER) IIIIIO Innovation and therapeutic focus • • Further raise innovation bar for Diabetes treatment Regulatory submission of once-weekly insulin icodec Completion of phase 3 trial PIONEER PLUS Completion of phase 1/2 trials with GLP-1/GIP Develop superior treatment solutions for obesity Phase 3a trials REDEFINE 2 & 3 initiated with CagriSema Strengthen and progress Rare Disease pipeline . • • . Somapacitan approved in the US for GHD in children CRL received for concizumab in the US Establish presence in Other serious chronic diseases Phase 1 trials initiated with cell therapy treatment 1Scope 1,2 and partial scope 3 limited to CO2 emissions from business flights and product distribution; 2MAT (Moving annual total) value market share VP: Vice president; CER: Constant exchange rates; CRL: Complete Response Letter; US: United States; GHD: Growth Hormone Deficiency; GIP: Gastric inhibitory polypeptide; GLP-1: Glucagon Like Peptide 1 Note: The strategic aspirations are not a projection of Novo Nordisk's financial outlook or expected growth Financials Sales growth of 25% (CER) and operating profit growth of 28% (CER) Operational leverage reflecting sales growth Free cash flow of DKK 24.8 billion and DKK 23.5 billion returned to shareholders#4Strategic Aspirations 2025 | Today with emphasis on Innovation and therapeutic focus Purpose and sustainability (ESG) لك Commercial execution Progress towards zero environmental impact Being respected for adding value to society Being recognised as a sustainable employer Strengthen Diabetes leadership - aim at global value market share of more than 1/3 More than 25 billion DKK in Obesity sales by 2025 Secure a sustained growth outlook for Rare disease CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease. Note: The strategic aspirations are not a projection of Novo Nordisk's financial outlook or expected growth. Financials therapeutic focus Innovation and OIIIII • Further raise the innovation-bar for diabetes treatment Develop a leading portfolio of superior treatment solutions for obesity Strengthen and progress the Rare disease pipeline Establish presence in Other serious chronic diseases focusing on CVD, NASH and CKD Deliver solid sales and operating profit growth ⚫ Drive operational efficiencies across the value chain to enable investments in future growth assets ⚫ Deliver free cash flow to enable attractive capital allocation to shareholders#5Today's speakers Martin Holst Lange Executive Vice President and Head of Development Stephen Charles Langford Gough Senior Vice President and Global Chief Medical Officer#6Agenda Introduction Insulin Daniel Bohsen & Martin Holst Lange GLP-1 in diabetes GLP-1 in obesity Q&A Insulin Icodec CagriSema in diabetes Oral semaglutide in diabetes Oral semaglutide in obesity Semaglutide 2.4 mg: STEP HFPEF Stephen Gough Martin Holst Lange Stephen Gough Stephen Gough Martin Holst Lange All O novo nordisk#7Since ADA 2022, progress has been made across the Novo Nordisk pipeline Higher doses injectable sema ph. 2 initiation A American Diabetes Association. ND SCIENTIFIC 82" SESSIONS NEW ORLEANS, LA | JUNE 5-7,2022 Acquisition of Forma Therapeutics Inc. Ph. 1 initiated with once-weekly oral semaglutide Concizumab ph. 3 completion Ph. 1 trials initiated in NASH utilising the siRNA platform 2023 Oral Sema 25/50 mg ph. 3 results Sogroya® US approval FHD with cell therapy in heart failure and Parkinson's disease 83rd Scientific Sessions SAN DIEGO, CA/HYBRID JUNE 23-26, 2023 NNC6019 ATTR ph. 2 initiation NDec ph. 2 initiation CagriSema T2D CagriSema Ph. 3a ph. 2 completed initiated Mim8 Ph.3 treatment initiation Completion of final Icodec ph. 3 trial Ph. 3 initiated with semaglutide 7.2 mg Oral GLP-1/ GIP co-agonist ph. 1 completed Ziltivekimab HFPEF ph. 3 initiation Icodec submission Diabetes care: GLP-1 Diabetes care: Insulin Rare disease T2D: Type 2 diabetes; Sema: Semaglutide; Ph: Phase FHD: First human dose; siRNA: Silencing RNA; HfPEF: Heart failure with preserved ejection fraction Note: Timeline non-exhaustive Obesity care Oral semaglutide 50 mg ph. 3 read- out Other serious chronic disease Other#8Agenda Introduction Insulin Daniel Bohsen & Martin Holst Lange GLP-1 in diabetes GLP-1 in obesity Insulin Icodec CagriSema in diabetes Oral semaglutide in diabetes Oral semaglutide in obesity Semaglutide 2.4 mg: STEP HFPEF Stephen Gough Martin Holst Lange Stephen Gough Stephen Gough Martin Holst Lange Q&A All O novo nordisk O#9Diabetes is a serious chronic disease requiring treatment intensification over time Diabetes is associated with multiple comorbidities Despite many new treatment options, many patients eventually need insulin The burden of treatment may be a barrier for good glycaemic control Macrovascular • Includes angina, CAD, MI, stroke, PAD, CHF, and CKD Microvascular • Retinopathy . ⚫ Nephropathy Neuropathy A 0.4% HbA1c reduction is associated with reductions of¹: 10% death related to diabetes 7% all cause mortality from PVD • 21% amputation or death B-cell function Diet and exercise Time OAD GLP-1 Insulin • 50% of patients needing insulin delay initiation by an average of 15 months due to needle aversion, anxiety over insulin and fear² • >90% of physicians and patients have a wish for good glycaemic control with insulin not injected every day³ 'Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study - PMC (nih.gov) - Linear relationship inferred, to estimate the point estimate with a 0.4% decrease in A1c. 2 Unpublished Novo Nordisk market research. ³Peyrot M et al. Diabet Med. 2012;29(5):682-689. CAD: Coronary artery disease; MI: Myocardial infarction; PAD: Peripheral arteries disease; CHF: Congestive heart failure; CKD: Chronic kidney disease; OAD: Oral anti diabetics; GLP-1: Glucagon-like peptide-1; PVD: Peripheral vascular disease#10Once-weekly insulin icodec appeared to be effective and to have a safe profile in the phase 3 ONWARDS programme ONWARDS 1 BASAL INITIATION 522 ONWARDS 3 BASAL INITIATION ONWARDS 5 BASAL INITIATION ONWARDS 2 BASAL SWITCH ONWARDS 4 BASAL/BOLUS SWITCH 26 ONWARDS 6 BASAL/BOLUS SWITCH 262 Trial duration (weeks) 26 52 26 (Full trial: 78 weeks) Baseline HbA1c (%) Non-inferiority confirmed 8.5% ✓ 8.5% ✓ 8.9% 8.1% ✓ 8.3% (Full trial: 52 weeks) 7.6% ✓ Superiority confirmed Estimated change from baseline in HbA1c (%) -0.47% -0.51% -0.71% -0.93%* -1.16% -1.18% -1.55%*-1.35% *-1.36% -1.31% 19.93 -1.57%* -1.68%* * 10.37 Hypoglycaemia event 0.30 0.16 rates¹ 0.31 0.15 5.64 5.62 0.19 0.14 0.73 0.27 Insulin-treated type 2 diabetes Type 1 diabetes Once-daily insulin degludec Once-daily basal insulins Insulin-naïve type 2 diabetes In people with type 2 diabetes: No statistical difference in estimated hypoglycaemia events Once-weekly insulin icodec Once-daily insulin glargine U100 *Statistically significant. 1 Severe or clinically significant hypoglycaemia events (blood glucose <3 mmol/L) per patient year, included for end of trial/end main phase in-trial. 2 Duration refers to trial main phase. ONWARDS 1: QW insulin icodec vs QD insulin glargine U100 both with non-insulin anti-diabetic treatment in insulin-naïve people with T2D; ONWARDS 2: QW insulin icodec vs QD insulin degludec in people with T2D switching from a QD insulin; ONWARDS 3: QW insulin icodec vs QD insulin degludec in insulin-naïve people with T2D; ONWARDS 4: QW insulin icodec vs QD insulin degludec both with mealtime insulin in people with T2D treated with basal and bolus insulin; ONWARDS 5: QW insulin icodec vs QD basal insulin with an app providing dosing recommendation in insulin-naïve people with T2D; ONWARDS 6: QW insulin icodec vs QD insulin degludec both with mealtime insulin in people with T1D T1D: Type 1 diabetes; T2D: Type 2 diabetes. Note: Overview refer to primary end-points in main phases of trials#11ONWARDS 1 compared insulin icodec with insulin glargine U100 in people with T2D initiating basal insulin R 1:1 ONWARDS 1 enrolled 984 patients with Type 2 Diabetes Once-weekly insulin icodec ± non-insulin anti-diabetic drugs Once-daily insulin glargine U100 ± non-insulin anti-diabetic drugs Main phase Objective: To confirm the efficacy and safety of once-weekly insulin icodec in insulin-naïve patients with type 2 diabetes Primary endpoint: • Change in HbA1c from baseline to week 52 Extension phase: A 26-week extension included in the trial design to assess long-term safety in people with T2D Inclusion criteria: + 52 Extension weeks phase 78 weeks • T2D treated with OADs* ± GLP-1 RA s.C. • Age ≥18 years · HbA1c 7-11% *Pre-trial all OADS including oral GLP-1s are allowed but SU and glinides are to be discontinued at randomisation T2D: Type 2 diabetes; R: Randomisation; OAD: Oral anti Diabetics; s.c.: subcutaneous; BMI: Body mass index; GLP-1: Glucagon-like peptide-1 BMI ≤40 kg/m2#12Once-weekly insulin icodec showed HbA1c reduction of -1.55% after 78 weeks of treatment in phase 3 trial ONWARDS 1 Greater reduction in HbA1c after 78 weeks with insulin icodec Overall hypoglycaemia in the trial Change in HbA1c (%-points) 0.0 -0.4 -0.8 -1.2 -1.6 Mean baseline HbA1c: 8.5% On treatment N Once-weekly insulin icodec Once-daily insulin glargine U100 (%) E R N (%) E R Level 2: Clinically significant hypo 61 (12.4) 226 0.30 66 (13.4) 114 0.15 Level 3: 1 0.2 1 0.001 6 (1.2) 7 0.009 Severe hypo -1.44% -1.55% Level 3 or 2: Severe or 61 (12.4) 227 0.30 70 clinically 0 (14.2) 121 0.16 significant hypo -2.0 0 10 18 26 36 44 52 62 70 78 78* Once-weekly insulin Icodec Once-daily insulin glargine U100 Note: Observed data are in-trial. Week 78* is estimated mean change in HbA1c based on ANCOVA with missing data derived from multiple imputation Note: Clinically significant hypoglycaemia (level 2): Plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by blood glycose meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is on-treatment. N: Number of patients with one or more events; %: Percentage of patients with one or more events; E: Number of events; R: Rate (number of events per patient year of exposure; Hypo: Hypoglycaemia#13In the trial, more patients on insulin icodec reached HbA1c target without hypoglycaemia and a longer TIR vs insulin glargine U100 Achievement of HbA₁c target after 78 weeks without hypoglycaemia¹ 54.5%* 1c Statistically significantly longer TIR for insulin icodec vs insulin glargine U100 measured with CGM from week 74 to 78 % of patients 46.4% 7.6% 21.1% 70.2%* 10.3% 24.1% 64.8% Once-weekly insulin icodec Once-daily insulin glargine U100 -0.3% -0.8% Once-weekly insulin icodec 0.2% 0.6% EOR=1.4 [1.06 to 1.80] 95% CI < 54mg/dL 54-<70mg/dL 70-180mg/dL >180-250mg/dL Once-daily insulin glargine U100 >250 mg/dL Achievement of HbA₁ target <7.0% without hypoglycaemia¹ Time in range • • Statistically significantly more participants achieved the HbA1c target without severe or clinically significant hypoglycaemia with insulin icodec compared to insulin glargine U100 70-180 mg/dL from week 74 to week 78 was 70.2% with once- weekly insulin icodec and 64.8% with once-weekly insulin glargine, statistically significant difference in favor of once-weekly insulin icodec vs once-daily insulin glargine U100 1 Specifically an HbA1c <7% without level 2 or 3 hypoglycaemic episodes during the prior 12 weeks; * Statistically significant difference in favour of insulin icodec. Note: The binary response after 78 weeks is analysed using a binary logistic regression model (logit link) with treatment and region as fixed factors, and the baseline HbA1c value as covariate. For TIR: Time spent is defined as 100 times the number of recorded measurements in a given range, divided by the total number of recorded measurements TIR: Time in range; CGM, continuous glucose monitor; CI: Confidence interval; EOR: Estimated odds ratio#14ONWARDS 5 included real-world elements and compared once- weekly insulin icodec with once-daily basal insulins in T2D Onwards 5 enrolled 1085 patients with Type 2 Diabetes Once-weekly insulin icodec + dosing guide app ± non-insulin anti-diabetic drugs Once-daily basal insulin analogues R 1:1 ± non-insulin anti-diabetic drugs 52 Weeks 5 weeks follow-up Objective: • To confirm the efficacy of HbA1c and safety of insulin icodec with a dosing guide app providing dosing recommendation vs once-daily basal insulin analogues, both in combination with any non-insulin antidiabetic medication in insulin-naïve T2D patients Trial design: The trial included real-world elements to reflect real-world insulin use with fewer planned site visits, no upper limit on HbA1c and minimal exclusion criteria. Key endpoints: • Change in HbA1c • Patient Related Outcomes (PROs) T2D: Type 2 diabetes; R: Randomisation. Once-daily basal insulin analogues include insulin degludec and insulin glargine U100 and U300 • Level 2 and 3 hypoglycaemia events Inclusion criteria: Insulin-naïve people with type 2 diabetes No limitations on use of oral antidiabetic treatments Age ≥18 years, HbA1c > 7.0%#15In the trial, insulin icodec appeared to have a safe profile and showed superior HbA1c reduction vs daily basal insulin analogues Superior reduction in HbA1c from baseline to 52 weeks Overall hypoglycaemia in the trial Change in HbA1c (%-points) 0.0 -0.4 -0.8 -1.2 -1.6 -2.0 0 13 Mean baseline HbA1c: 8.9% 26 39 On treatment N Once-weekly insulin icodec Once-daily basal insulin analogues (%) E RN (%) E R Level 2: Clinically significant Hypo* 64 (11.8) 104 0.19 42 (7.8) 76 0.13 -1.31 Level 3: 4 (0.7) 5 0.01 Severe Hypo* -1.68 Level 3 or 2: Severe or 64 (11.8) 104 0.19 45 45 (8.4) 81 0.14 clinically significant Hypo* 52 52* Time since randomisation (weeks) Once-weekly insulin icodec Once-daily basal insulin analogues Note: Observed data are in-trial. Week 52* is estimated mean change in HbA1c based on ANCOVA with missing data derived from multiple imputation. Insulin icodec was in combination with a dosing guide app. Once-daily basal insulin analogues include insulin degludec and insulin glargine U100 and U300 Note: Clinically significant hypoglycaemia (level 2): Plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by blood glycose meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is on-treatment. N: Number of patients with one or more events; %: Percentage of patients with one or more events; E: Number of events; R: Rate (number of events per patient year of exposure; Hypo: Hypoglycaemia#16Insulin icodec showed superiority in both patient reported outcomes endpoints vs daily basal insulins in ONWARDS 5 DTSQ total treatment score: Health-related quality of life questionnaire Treatment satisfaction score: 1-6 TRIM-D compliance domain score: Compliance questionnaire Treatment satisfaction score: 1-100 4.68 Treatment difference 0.781 3.90 90.42 Treatment difference 3.042 87.37 Once-weekly insulin icodec Once-daily basal insulin analogues Once-weekly insulin icodec. Once-daily basal insulin analogues Estimated mean change from baseline Estimated mean difference at week 52 1Treatment difference = 0.78 [0.10;1.47]95% CI, P value: 0.0247 2Treatment difference = 3.04 [1.28;4.81]95% CI, P value: 0.0007 DTSQ: Diabetes Treatment Satisfaction Questionnaire; TRIM-D: Treatment-Related Impact Measure Diabetes Note: Insulin icodec was in combination with a dosing guide app. Once- daily basal insulin analogues include insulin degludec and insulin glargine U100 and U300#17Insulin icodec has the potential to reduce treatment burden for both insulin naïve people or those switching from a daily basal Icodec has the potential to reduce treatment burden Once daily basal insulin Once-weekly insulin icodec Icodec titration scheme in type 2 diabetes 180 SMTWTFS BC SMTWTFS 180 Many injections per week (>365 per year) One injection per week (52 per year) Note: Graphic on left illustrates conceptual differences Naïve to insulin treatment 180 Single Starting Dose 70 units Prior basal insulin treatment Single Starting Dose 10.5 x Daily Basal Insulin Dose Second Dose Daily Basal Insulin Dose x 7#18Insulin: Key take-aways Despite many new treatment options, many patients eventually need insulin treatment The burden of treatment and daily injections can be a barrier for good glycaemic control Insulin icodec appears to have a superior efficacy profile with added weekly convenience and a low rate of hypoglycemia* Overall, insulin icodec has the potential to be an ideal starter insulin for people with T2D *Less than one event per year for level 2 or 3 hypoglycemia in the insulin naïve and in the basal switch T2D population T2D: Type 2 Diabetes C O O O novo nordisk#19Agenda Introduction Insulin GLP-1 in diabetes GLP-1 in obesity Q&A Insulin Icodec CagriSema in diabetes Oral semaglutide in diabetes Oral semaglutide in obesity Semaglutide 2.4 mg: STEP HFPEF Daniel Bohsen & Martin Holst Lange Stephen Gough Martin Holst Lange Stephen Gough Stephen Gough Martin Holst Lange All O novo nordisk#20GLP-1 RAs have proven positive effects beyond glycaemic control in T2D and may hold further potential Glucagon-like peptide-1 receptor agonists to expand the healthy lifespan: Current and future potentials Frederik Flindt Kreiner | Bernt Johan von Scholten | Peter Kurtzhals | Stephen Charles Langford Gough Global Medical Affairs, Novo Nordisk A/S, Søborg. Denmark Correspondence Stephen Charles Langford Gough, Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark. Email: [email protected] Abstract To help ensure an expanded healthy lifespan for as many people possible world- wide, there is a need O prevent or manage a number of prevalent chronic diseases directly and indirectly closely related to aging, including diabetes and obesity. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have proven beneficial in type 2 diabetes, are amongst the few medicines approved for weight management, and are also licensed for focused cardiovascular risk reduction. In addition, strong evi- dence suggests several other beneficial effects of the pleiotropic peptide hormone, including anti-inflammation. Consequently, GLP-1 RAS are now in advanced clinical development for the treatment of chronic kidney disease, broader cardiovascular risk reduction, metabolic liver disease and Alzheimer's disease. In sum, GLP-1 RAS are po sitioned as one of the pharmacotherapeutic options that can contribute to addressing the high unmet medical need characterising several prevalent aging-related diseases, potentially helping more people enjoy a prolonged healthy lifespan. KEYWORDS Alzheimer's disease, cardiovascular diseases, chronic kidney diseases, diabetes mellitus, glucagon-like peptide-1, healthy aging, non-alcoholic steatohepatitis, obesity 1 INTRODUCTION Increased age is associated with trailty and diseases of varying sever- ities, and for many, the hope of a long and healthy lifespan therefore becomes elusive. Nevertheless, overall life expectancy has increased markedly during the past decades, owing to a large extent to the in- troduction medicines such as statins and anti-hypertensives. These and newer generation drugs have resulted in a lower prevalence and severity of age-related illnesses such as cardiovascular disease (CVD) To sustain and reinforce this positive trend and help ensure a pro- longed healthspan for more people across the world, novel pharmaco- therapeutics and optimal use of existing options are arguably needed. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are ample of a drug class with proven or potential benefits across a range of prevalent age-related conditions and complications (Müller et al., 2019). Originally developed to manage blood glucose levels in type 2 diabetes (T2D), GLP-1 RAs have subsequently been confirmed to have marked benefits on body weight and CVD risk. Furthermore, evidence from Abbreviation CHIP, clonal haematopoiesis of indeterminate potential CKD, chronic kidney disease; CVD, cardiovascular CVOT, cardiovascular outcomes trial; DKD, diabetic kidney disease, DM, diabetes mellitus: GP, gastric inhibitory peptide GLP-1, glucagon-like peptide-1: GLP-1R glucagon-like peptide-1 receptor, HFPEF, heart failure with preserved ejection fraction; MACE major adverse cardiovascular event; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic hepatocteatosis; RA, receptor agonist: T2D, type 2 diabetes. This is an open access and _ is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in provided the original work is properly cited. © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. any medium, Proven GLP-1 RA effects in T2D Glycaemic control Weight loss CV risk reduction Hypothesized GLP-1 RA effects GD Chronic kidney disease Alzheimer's disease GLP-1 RA: Glucagon like peptide-1 receptor agonist; T2D: Type 2 diabetes; CV: Cardiovascular Metabolic liver syndrome Peripheral artery disease#21GLP-1 RAS recommended as first line treatment for people with T2D with established ASCVD or with multiple CV risk factors Updated ADA/EASD diabetes treatment guidelines Lifestyle management Goal: Cardiorenal risk reduction in high-risk T2D patients (on top of CV SoC) Goal: HbA1c and weight management ASCVD or indicators of high risk Glycaemic management GLP-1 with proven CVD benefit OR SGLT-2i with proven CVD benefit Metformin OR combination therapy with adequate efficacy to reach and maintain goals (intermediate - very high) Very high: Semaglutide mentioned for glucose lowering efficacy HF with documented HFrEF or HFPEF CKD SGLT-2i with proven HF benefit Weight management Set individualized weight management goals When choosing glucose-lowering therapies consider regimen with high efficacy SGLT-2i with primary evidence of reducing CKD progression THEN GLP-1 with proven CVD benefit Very high: Semaglutide mentioned for weight loss efficacy If additional cardiorenal risk reduction or glycaemic lowering needed If HbA1c above target, identify barriers to reach treatment goals Sources: Adapted from: "Standards of Medical Care in Diabetes - 2022" Supplement 1, p.133; diabetes.org. American Diabetes Association & "Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)", Davies MJ. Et al, Diabetes Care 2022 (https://doi.org/10.2337/dci22-0034) GLP-1 RA: Glucagon like peptide-1 receptor agonist; ADA: American Diabetes Association; EASD: European Association for the Study of Diabetes; T2D: Type 2 diabetes; CV: Cardio vascular; SoC: Standart of care; ASCVD: Atherosclerotic cardiovascular disease; CVD: Cardiovascular disease; SGLT-2i: Sodium/glucose co-transporter-2 inhibitors; HF: Heart failure: HFrEF: Heart failure with reduced ejection fraction; HFPEF: Heart failure with preserved ejection fraction; CKD: Chronic kidney disease#22Phase 2 trial for CagriSema in people with type 2 diabetes was successfully completed in Q3 2022 Exploratory phase 2a trial of CagriSema in 92 patients with T2D Cagrilintide 2.4 mg + semaglutide 2.4 mg R Cagrilintide 2.4 mg + placebo 1:1:1 Semaglutide 2.4 mg + placebo Dose escalation Treatment maintenance Follow up 16 weeks 5 weeks 16 weeks Objective: • To compare the efficacy and safety of CagriSema vs its individual components in patients with T2D Primary endpoint: Change from baseline to week 32 in HbA1c Secondary endpoints: • • • Change from baseline to week 32 in body weight Safety CGM: Mean glucose levels, time in range Inclusion criteria: . Type 2 diabetes • HbA1c 7.5-10.0% • Metformin +/- SGLT-2i • BMI ≥27 kg/m2 T2D: Type 2 diabetes; R: Randomisation; BMI: body mass index; CGM: Continuous glucose monitoring; SGLT-2i: Sodium/glucose co-transporter-2 inhibitors Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg#23Mean HbA1c reduction from baseline was -2.18 %-points and 89% reached HbA1c target when treated with CagriSema Higher HbA1c reduction with CagriSema compared to monocomponents Mean baseline HbA1c 8.4% Achievement of HbA1c target <7.0% after 32 weeks Change in HbA1c (%-points) 0.0 -1.0 -2.0 -3.0 0 4 812 20 20 Time since randomisation (weeks) CagriSema Semaglutide Cagrilintide -0.93 -1.79 -2.18 28 32 100 89% 00 80 % of patients Note: Data shown is trial product estimands. CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg 60 60 40 40 20 20 69% 33% CagriSema Semaglutide Cagrilintide More participants achieved the HbA1c target when treated with CagriSema compared to the monocomponents#24With CagriSema, time in range reached -90% at week 32 and mean glucose levels decreased by ~64 mg/dL Longer time in range for CagriSema vs semaglutide and cagrilintide CagriSema Semaglutide Cagrilintide 1.5% 8.8% 8.7% 10.0% 17.8% 23.8% 15.0% 22.6% 32.5% 36.2% 45.9% 43.5% 88.9% 32.6% 5.5% Time in range Time in range goes "beyond" HbA1c for detailed insights into glycemic control in people with diabetes Time in range (70-180 mg/dL) increased in all groups, reaching 88.9% with CagriSema at week 32 76.2% 71.7% 56.9% 0.1% 0.8% Baseline Week 32 0.1% Baseline 0.1% Week 32 0.6% Baseline 0.2% Week 32 <70 mg/dL 70-180 mg/dL >180-250 mg/dL >250 mg/dL Note: Data shown is trial product estimands Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg TIR: Time in range • Mean glucose levels Decreased from baseline to week 32 in all groups, reaching -63.9mg/dL for CagriSema, -43.6 mg/dL for semaglutide and -23.4 mg/dL for cagrilintide#25Mean weight loss was -15.6% and more than half of patients achieved ≥15% weight loss when treated with CagriSema Higher body weight reduction with CagriSema compared to semaglutide and cagrilintide alone Mean baseline body weight: 105.7 kg Change in body weight (%) -12 ထ + -5.1 -8.1 -15.6 -16 0 4 8 12 16 20 20 28 32 2 Time since randomisation (weeks) CagriSema Semaglutide Cagrilintide % of patients Categorical weight loss after 32 weeks of treatment 100 75 50 71.4% 25 23.3% 25 13.8% CagriSema Sema ≥10% body weight reduction Note: Data shown on weight loss over time is trial product estimands. Data on categorical weight loss is from post-hoc analysis (descriptive), from the on-treatment period. Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg. Sema: Semaglutide; Cagri: Cagrilintide 53.6% 6.7% 0% Cagri CagriSema Semal Cagri ≥ 15% body weight reduction#26In the phase 2 trial, CagriSema appeared to have a safe and well- tolerated profile AES Severity of AEs Mild Moderate Severe Gastrointestinal adverse events Serious AES AEs leading to drug withdrawal CagriSema 2.4 mg (n = 31) Semaglutide 2.4 mg (n = 31) Cagrilintide 2.4 mg (n = 30) n % n % n % 21 67.7 22 71.0 24 80.0 18 58.1 13 14 45.2 16 36 41.9 20 66.7 51.6 13 43.3 0 0.0 1 3.2 1 3.3 18 58.1 10 32.3 10 33.3 0 0.0 2 6.5 4 13.3 0 0.0 1 3.2 0.0 Gastrointestinal adverse events were all mild or moderate in severity and the majority occurred during dose escalation GLP-1: Glucagon like peptide-1; AE: Adverse event Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg#27Phase 3 trial programme in type 2 diabetes, REIMAGINE, expected to initiate in second half of 2023 CagriSema characteristics REIMAGINE 1 vs placebo CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and semaglutide 2.4 mg REIMAGINE 2 FDC trial REIMAGINE 3 Add-on to insulin Phase 3a programme with CagriSema in T2D: Aims to confirm efficacy and safety across four global trials REIMAGINE 4 H2H vs tirzepatide REDEFINE 3 • Global phase 3 trial programme • 180 patients with T2D 40-week vs. placebo • Primary endpoint: HbA1c 2700 patients with T2D, MET +/- SGLT-2i 68-week vs. semaglutide, cagrilintide and placebo • Primary endpoint: HbA1c and bodyweight • • 270 patients with T2D, Basal insulin +/- MET 40-week vs. placebo • Primary endpoint: HbA1c 1000 patients with T2D, MET +/- SGLT-2i 68-week vs. tirzepatide • Primary endpoint: HbA1c and bodyweight • Expected completion during 2025/2026 4000 patients¹ CVOT - shared with obesity programme • Event driven O Primary endpoint: 3-point MACE 2023 2024 2025 1 65% of patients with T2D, 35% without T2D FDC: Fixed dose combination; T2D: Type 2 Diabetes; H2H: Head-to-head; CVOT: Cardiovascular outcomes trial; 3P: Three point; MACE: Major adverse cardiovascular event; MET: Metformin; SGLT-2i: sodium-glucose co-transporter-2 inhibitor Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg 2026#28PIONEER PLUS with oral semaglutide in people with type 2 diabetes was successfully completed in Q2 2023 PIONEER PLUS enrolled 1606 patients with T2D Oral semaglutide 50 mg R Oral semaglutide 25 mg 1:1:1 Oral semaglutide 14 mg • Objective: To compare the safety and efficacy of once daily oral semaglutide 25 mg and 50 mg with oral semaglutide 14 mg in people with T2D Primary endpoint: Change from baseline to week 52 in HbA1c Secondary confirmatory endpoints: Change from baseline to week 52 in body weight Key Inclusion criteria: 68 weeks 5 weeks follow-up • Type 2 diabetes • HbA1c 8.0-10.5% T2D: Type 2 diabetes; R: Randomisation; BMI: body mass index; SGLT-2i: Sodium/glucose co-transporter-2 inhibitors BMI ≥25 kg/m2 Stable dose of 1-3 OADs (metformin, SU, SGLT-2i or DPP-4i)#29Oral semaglutide 25 and 50 mg demonstrated statistically significant and superior reduction in HbA1c compared to 14 mg 0.0 Superior reduction in HbA1c from baseline to 52 weeks Mean baseline HbA1c: 9.0% 100 Achievement of HbA1c target <7.0% after 52 weeks Change in HbA1c (%-points) -0.4 -0.8 -1.2 -1.6 -1.5 % of patients 80 60 60 40 40 -1.9 20 20 -2.0 -2.2 0 -2.4 0 4 8 12 16 20 Time since randomisation (weeks) 26 32 38 44 52 52* Oral sema 14 mg Oral sema 25 mg Oral sema 50 mg 74.2% 59.6% 47.5% Oral sema 14mg Oral sema 25mg Oral sema 50mg More participants achieved the HbA₁c target after 52 weeks with oral semaglutide 25 and 50 mg compared to 14 mg Note: Observed data are on-treatment. Week 52* is the HbA1c change using the trial product estimand. HbA1c targets are shown with trial product estimand data Sema: Semaglutide#30Change in body weight (%) Oral semaglutide 25 and 50 mg demonstrated statistically significant higher weight loss vs 14 mg in the PIONEER plus trial Higher body weight reduction with oral semaglutide 25 mg and 50 mg compared to 14 mg Mean baseline body weight: 96.4kg 0.0 -2.0 -4.0 -6.0 -8.0 -10.0 04 8 12 16 20 26 32 Time since randomisation (weeks) Oral sema 14 mg Oral sema 25 mg -4.5% -7.0% % of patients 100 75 Categorical weight loss after 52 weeks of treatment 50 44.1% 25 75.7% 63.2% 43.9% 32.4% 15.7% 0 -9.2% Oral sema Oral sema Oral sema Oral sema 38 44 52 52* 14 mg 25 mg 50 mg 14 mg Oral sema 25 mg Oral sema ≥5% body weight reduction 50 mg ≥10% body weight reduction Oral sema 50 mg Note: Observed data are on-treatment. Week 52* is the body weight change using the trial product estimand. Sema: Semaglutide#31The safety profile of oral semaglutide 25 and 50 mg was generally consistent with the GLP-1 receptor agonist drug class Oral semaglutide Oral semaglutide 14 mg (n = 534) 25 mg (n = 534) Oral semaglutide 50 mg (n = 534) n % n % n % AEs 404 (75.7) 422 (79.0) 428 (80.1) Gastrointestinal adverse events 225 (42.1) 282 (52.8) 286 (53.6) Serious AEs 53 (9.9) 57 (10.7) 44 (8.2) AEs leading to drug withdrawal 54 (10.1) 66 (12.4) 68 (12.7) GLP-1: Glucagon like peptide-1; AE: Adverse event; T2D: Type 2 diabetes Safety: • Majority of gastrointestinal adverse events were mild or moderate in severity The majority occurred during dose escalation In the trial, oral semaglutide 25 and 50 mg appeared to have a safe and well-tolerated profile#32GLP-1 diabetes: Key take-aways: GLP-1 RA's have demonstrated several benefits and are recommended as first line treatment for some people with T2D in international treatment guidelines In the phase 2 trial, CagriSema showed improved reduction of HbA1c and of body weight as well as longer time in range vs monocomponents CagriSema appeared to have a safe and well-tolerated profile. Phase 3 in T2D is expected to be initiated during H2 of 2023 Based on the efficacy profile in PIONEER PLUS, oral semaglutide 25 and 50 mg may provide the option for patients to progress to higher doses if additional glycaemic control or weight loss is needed GLP-1 RA: Glucagon like peptide-1 receptor agonist; T2D: Type 2 diabetes Note: CagriSema is a fixed dose combination of injectable cagrilintide 2.4 mg and injectable semaglutide 2.4 mg C O O O novo nordisk#33Agenda Introduction Insulin Daniel Bohsen & Martin Holst Lange GLP-1 in diabetes GLP-1 in obesity Q&A Insulin Icodec CagriSema in diabetes Oral semaglutide in diabetes Oral semaglutide in obesity Semaglutide 2.4 mg: STEP HFPEF Stephen Gough Martin Holst Lange Stephen Gough Stephen Gough Martin Holst Lange All O novo nordisk#34OASIS 1 with oral semaglutide 50 mg in people with overweight or obesity has been successfully completed OASIS 1 enrolled 667 patients with overweight or obesity Oral Semaglutide 50 mg* R Placebo* 1:1 68 Weeks Lifestyle intervention 7 weeks follow-up Objective: • To compare the safety and efficacy of 50 mg oral semaglutide with placebo in people with overweight or obesity without T2D Co-primary endpoints: • Percentage change in body weight from baseline to week 68 Achievement of ≥5% weight loss from baseline at week 68 Confirmatory secondary endpoints: • Achievement of ≥10%, ≥15% and ≥20% weight loss from baseline at week 68 Inclusion criteria: • ⚫ BMI: ≥27 kg/m² with ≥ 1 weight-related comorbidity, or • BMI: ≥30 kg/m² • . Weight-related comorbidities are hypertension, dyslipidaemia, obstructive sleep apnoea and CVD • ≥1 self-reported dietary weight loss effort *As an adjunct to a reduced-calorie diet and increased physical activity in adults with obesity or with overweight and weight-related comorbidities (Weight-related comorbidities are hypertension, dyslipidaemia, obstructive sleep apnoea and CVD) T2D: Type 2 diabetes; R: Randomisation; BMI: body mass index#35Oral semaglutide 50 mg in overweight or obesity demonstrated superior body weight reduction in the OASIS 1 trial vs placebo OASIS 1 showed significantly greater weight loss compared to placebo 0 Change in body weight (%) -15 -12 9 -6 ώ Mean baseline body weight: 105.4kg Categorical weight loss % at week 68 100 89.2 -1.8 % of patients 80 88 60 60 40 40 20 20 24.5 74.7 58.5 37.2 11.8 5.3 -17.4 2.4 -18 048 12 16 20 28 36 44 52 60 Time since randomisation (weeks) Oral sema 50 mg Placebo 0 68 68* ≥5% ≥10% ≥15% ≥20% Oral sema 50 mg Placebo Note: Observed data are on-treatment. Week 68* is the body weight change using the trial product strategy Sema: Semaglutide#36The safety profile of oral semaglutide 50 mg was generally consistent with the GLP-1 receptor agonist drug class Oral semaglutide 50 mg Placebo (n = 333) (n = 334) n % n % . AEs 307 (91.9) 285 (85.6) • Gastrointestinal adverse events 268 (80.2) 154 (46.2) Serious AEs 32 (9.6) 29 (8.7) AEs leading to drug withdrawal 19 (5.7) 12 (3.6) GLP-1: Glucagon like peptide-1; AE: Adverse event Safety: . Majority of gastrointestinal adverse events were mild or moderate in severity • The majority occurred during dose escalation In the trial, oral semaglutide 50 mg appeared to have a safe and well-tolerated profile.#37Phase 3 trial programme for oral semaglutide 50 mg in overweight or obesity, OASIS Oral semaglutide characteristics a Oral semaglutide 50mg: Semaglutide tablets in overweight or obesity • Once daily tablet Phase 3a programme with oral semaglutide 50 mg Aims to confirm efficacy and safety Submission in US and EU expected during 2023 The global launch of oral semaglutide 50 mg is contingent on portfolio prioritisations and manufacturing capacity BW: Body weight; T2D: Type 2 diabetes Focused phase 3 trial programme OASIS 1 . 667 patients 50 mg dose 68 week Primary endpoint: BW % 198 patients incl. T2D OASIS 2 . EAST ASIA • 68 week OASIS 3 China • Primary endpoint: BW % • . 200 patients incl. T2D 44 week Primary endpoint: BW % OASIS 4 25 mg dose 2022 ⚫ 300 patients 64 week Primary endpoint: BW % 2023 2024 2025#38Obesity is associated with multiple comorbidities, which may be improved with weight management Life expectancy decreases as BMI increases¹ Obesity related comorbidities² Normal BMI Almost 80% chance of reaching age 70 Mental ⚫ Depression Anxiety BMI 35-40 kg/m² ~60% chance of reaching age 70 BMI 40-50 kg/m² -50% chance of reaching age 70 Mechanical Asthma GERD Physical functioning • Incontinence Knee osteoarthritis Sleep apnea Chronic back pain Metabolic NAFLD Gallstones Infertility Type 2 diabetes Prediabetes Thrombosis Gout Cancers* CVD: • Stroke Dyslipidemia • Hypertension Coronary artery disease HFPEF *Including breast, colorectal, endometrial, oesophageal, kidney, ovarian, pancreatic and prostate 1 Prospective Studies Collaboration. Lancet. 2009;373:1083-96. 2 Adapted from Sharma AM. Obes Rev 2010;11:808-9; Guh DP et al. BMC Public Health 2009;9:88; Luppino FS et al. Arch Gen Psychiatry 2010;67:220-9; Simon GE et al. Arch Gen Psychiatry 2006;63:824-30; Church TS et al. Gastroenterology 2006;130:2023-30; Li C et al. Prev Med 2010;51:18-23; Hosler AS. Prev Chronic Dis 2009;6:A48. BMI: Body mass index; GERD: gastro-oesophageal reflux disease; HFPEF: heart failure with preserved ejection fraction; NAFLD: non-alcoholic fatty liver disease; CVD: Cardiovascular disease; HFPEF: Heart failure with preserved ejection fraction#39HFPEF compromises -50% of all HF cases, and -80% of HFPEF patients live with overweight or obesity Heart failure with preserved ejection fraction • Impaired filling capacity Stiff and thick ventricle LVEF ≥50% Approximately 26 million people have HFPEF and BMI>271,2 64m 32m 26m تھی Patients with HFPEF are under a great burden³ Higher mortality rate Higher risk of hospitalisation Higher burden of debilitating symptoms, physical limitations and poor quality of life The key goals of therapy³ Prolong survival Reduce hospitalisations Reduce symptoms; improve quality of life and functional status HF HFPEF Prevalence of HFPEF and BMI>27 1. Groenewegen A et al. Eur J Heart Fail 2020;22:1342-13561; Gurwitz JH et al. Am J Med 2013;126:393-400; 2. Haass M et al. Circulation 2011;4:324-331; Kitzman DW, et al. J Am Coll Cardiol 2016;68:200-203 3. Ponikowski P et al. Eur J Heart Fail 2016;18:891-975 LVEF: Left ventricular ejection fraction; HF: Heart failure; HFPEF: Heart Failure with preserved ejection fraction#40Phase 3 trial STEP HFPEF with semaglutide 2.4 mg has been successfully completed in Q2 2023 STEP HFPEF trial with 529 people with obesity and HFPEF Objective: STEP HFPEF • Evaluate the effect on HF specific symptoms, physical function and body weight compared with placebo Dual primary endpoints: Semaglutide 2.4 mg + SoC R Placebo + SoC 1:1 Dose escalation Treatment maintenance Follow up 16 weeks 36 weeks 5 weeks • Change in KCCQ from baseline to week 52 • Change in body weight from baseline to week 52 Key secondary endpoints: Change in 6MWD from baseline to week 52 Composite endpoint (all cause death, HHF, KCCQ, 6MWD) from baseline to week 52 Inclusion criteria: • BMI ≥30 kg/m2 • NYHA II-IV • Ejection fraction ≥45% R: Randomisation; HF: Heart Failure; HFPEF: Heart Failure with preserved ejection fraction; SoC: Standard of care; KCCQ: Kansas City Cardiomyopathy Questionnaire; 6MWD: 6-min walking distance; HHF: Heart failure hospitalization; NYHA: New York Heart Association classification#41The Kansas City Cardiomyopathy Questionnaire, a patient reported outcome, was primary endpoint in the STEP HFPEF trial Disease Symptoms Symptom domains Kansas City Cardiomyopathy Questionnaire¹ Function limitations Quality of life Functional limitation domains Quality of life domain Self efficacy Stability Symptom frequency Symptom burden Physical limitations Social limitations QoL score Dual primary endpoint: KCCQ clinical summary score KCCQ score interpretation² Health status Score 0 to 24 Very poor to poor Poor to fair 25 to 49 50 to 74 Fair to good 75 to 100 Good to excellent 1 Adapted from: Spertus JA. et al. JACC 2020; 76: 2379-2390; Kelkar AA et al. JACC Heart Fail 2016;4:165-175; Nassif ME et al. Circulation 2019;140:1463-1476 2. Enright PL. et al. Respir Care 2003; 48: 783-785. 2 Spertus JA, et al. JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Nov 17;76(20):2379-2390. HFPEF: Heart Failure with preserved ejection fraction; KCCQ: Kansas City Cardiomyopathy Questionnaire#42Semaglutide 2.4 mg demonstrated superior improvement on the primary endpoint of KCCQ-CSS vs placebo Superior improvement in KCCQ-CSS score in patients treated with semaglutide 2.4 mg Mean baseline KCCQ-CSS score: 56.7 20 20 16.6 Primary endpoints: • Key highlights KCCQ-CSS estimated treatment difference between semaglutide 2.4 mg and placebo of 7.8 Change in KCCQ-CSS (score) 15 10 5 20 36 Time since randomisation (weeks) 8.7 52 52* Semaglutide 2.4mg Placebo 1 Spertus JA, et al. JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Nov 17;76(20):2379-2390. KCCQ in perspective Clinicians' assessments of clinical change¹: • . • Small: +5 points Moderate-to-large: +10 points Large-to-very large: +20 points Patients' self-classifications of improvements¹: Minimal clinically important difference for 'little improvement': 4.5 points Note: Data shown is the treatment policy estimand. *Lines are based on observed data where the value denoted after 52 weeks is estimated mean value derived based on multiple imputation KCCQ-CSS: Kansas City Cardiomyopathy Questionnaire Clinical summary score#43Semaglutide 2.4 mg demonstrated superior reduction on the other primary endpoint of body weight vs placebo Clinically relevant and sustained weight loss in patients treated with semaglutide 2.4 mg Mean baseline body weight: 108.4 kg Change in body weight (%) -15 -10 J Primary endpoint: -2.6 -13.3 • -20 0 4 8 12 16 20 28 36 44 52 52* Time since randomisation (weeks) Placebo Key highlights Estimated treatment difference in body weight change between semaglutide 2.4 mg and placebo of -10.7% Safety: Overall, the safety profile in HFPEF patients is consistent with previous data for semaglutide 2.4 mg Semaglutide 2.4mg Note: Data shown is the treatment policy estimand. *Lines are based on observed data where the value denoted after 52 weeks is estimated mean value derived based on multiple imputation HF: Heart failure#44The ongoing STEP HFPEF-DM trial is to be included in the regulatory submission STEP HFPEF-DM trial with 610 people with obesity, HFPEF and T2D Semaglutide 2.4 mg + SoC R 1:1 Placebo + SoC Trial design and next steps Dual primary endpoints: • Change in KCCQ from baseline to week 52 • Change in body weight from baseline to week 52 Inclusion criteria: • BMI ≥30 kg/m2 • NYHA II-IV Ejection fraction ≥45% Dose escalation Treatment maintenance Follow up 16 weeks . HbA1c ≤10.0% 36 weeks 5 weeks Next steps: • Completion of STEP HFPEF-DM trial expected in H2 2023 • Combined regulatory submission of both trials in H1 2024 • Decision expected late 2024/early 2025 R: Randomisation; HF: Heart Failure; HFPEF: Heart Failure with preserved ejection fraction; SoC: Standard of care; KCCQ: Kansas City Cardiomyopathy Questionnaire; 6MWD: 6-min walking distance; NYHA: New York Heart Association classification#45GLP-1 obesity: Key take-aways: In OASIS 1, oral semaglaglutide 50 mg showed efficacy broadly on par with injectable semaglutide 2.4 mg A high unmeet need exists within obesity-related HFpEF Semaglutide 2.4 mg demonstrated superiority on the dual primary endpoint vs placebo in the STEP HFPEF trial C O O O novo nordisk#46sustainability Purpose and (ESG) Strategic aspirations 2025 • Progress towards zero environmental impact Being respected for adding value to society Being recognised as a sustainable employer ピ Commercial execution Strengthen Diabetes leadership - aim at global value market share of more than 1/3 More than 25 billion DKK in Obesity sales by 2025 Secure a sustained growth outlook for Rare disease CVD: Cardiovascular disease; NASH: Non-alcoholic steatohepatitis; CKD: Chronic kidney disease. Note: The strategic aspirations are not a projection of Novo Nordisk's financial outlook or expected growth. Financials ווון шо Innovation and therapeutic focus • Further raise the innovation-bar for diabetes treatment Develop a leading portfolio of superior treatment solutions for obesity Strengthen and progress the Rare disease pipeline Establish presence in Other serious chronic diseases focusing on CVD, NASH and CKD • Deliver solid sales and operating profit growth . Drive operational efficiencies across the value chain to enable investments in future growth assets • Deliver free cash flow to enable attractive capital allocation to shareholders#47Agenda Introduction Insulin Daniel Bohsen & Martin Holst Lange GLP-1 in diabetes Insulin Icodec GLP-1 in obesity Q&A CagriSema in diabetes Oral semaglutide in diabetes Oral semaglutide in obesity Semaglutide 2.4 mg: STEP HFPEF Stephen Gough Martin Holst Lange Stephen Gough Stephen Gough Martin Holst Lange All O novo nordisk O#48Investor contact information Share information Novo Nordisk's B shares are listed on the stock exchange in Copenhagen under the symbol 'NOVO B'. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. For further company information, visit Novo Nordisk on: www.novonordisk.com Novo Nordisk A/S Investor Relations Novo Alle 1 DK-2880 Bagsværd Investor Relations contacts Daniel Muusmann Bohsen David Heiberg Landsted Jacob Martin Wiborg Rode Mark Joseph Root (USA) +45 3075 2175 +45 3077 6915 +45 3075 5956 +1 848 213 3219 [email protected] [email protected] [email protected] [email protected] 10 August 2023 Upcoming events Financial statement for the first six months of 2023 02 November 2023 Financial statement for the first nine months of 2023 31 January 2024 Financial statement 2023

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