Investor Presentaiton
References and notes for slide 6
The multifactorial effects of GLP-1s
Pancreas
Beta-cell function2
Beta-cell apoptosis?
Insulin biosynthesis?
Glucose-dependent insulin secretion²
Glucose-dependent glucagon secretion²
Liver
Endogenous glucose production¹¹
Hepatic insulin sensitivity11
De novo lipogenesis"
Lipotoxicity
Heart
CV risk³
Fatty acid metabolism*
Cardiac function
Systolic blood pressure
Inflammation"
Atherosclerotic plaque
progression³
Brain
Body weight
Food intake?
Satiety.
Steatosis12
Investor presentation
ADA 2019
Slide 36
ADA/EASD diabetes treatment guidelines for second-
line treatment with established ASCVC or CKD1
First-line therapy is metformin and lifestyle management.
If HbA above target, proceed as below
Established ASCVD or CKD
Without
NO
established
ASCVD or
YES
ASCVD predominates
GLP-1
with proven CVD
benefit*
EITHER/
OR
CKD
SGLT2
with proven CVD
benefit*,
if eGFR adequate
HF OR CKD
predominant
Incretin system
Replacement of deficient
GLP-1 response¹0
1 Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus
Report by the American Diabetes Association (ADA) and the European
Association for the Study of Diabetes (EASD); 2 Campbell JE, DJ Drucker.
Cell Metab. 2013;17:819-837; 3 Marso SP et al. N Engl J Med.
2016;375:311-322; 4 Ryan D, Acosta A. Obesity. 2015;23:1119-1129; 5
Hogan AE et al. Diabetologia. 2014;57:781-784; 6 Baggio LL, Drucker DJ.
J Clin Invest. 2014;124:4223-4226; 6 Bagger JI et al. Clin Endocrinol
Metab. 2015;100:4541-4552; 8 Flint A et al. J Clin Invest. 1998;101:515-
520; 9 Blundell J et al. Presented at the 76th Scientific Sessions of the
American Diabetes Association June 10-14, 2016, New Orleans, Louisiana,
USA: Oral Presentation 23-OR; 10 Tong J, D'Alessio D. Diabetes.
2014;63:407-409; 11 Armstrong MJ, et al. J Hepatol. 2016;64:399-408;
12 Armstrong MJ, et al. Lancet. 2016;387:679-90.
If HbA1c above target
If further intensification is required or patient is now unable to
tolerate GLP-1 and/or SGLT2, choose agents demonstrating CV
safety...
SIMPLIFIED
ILLUSTRATION
*Proven CVD benefit means it has label indication of reducing CVD
events. For GLP-1 strongest evidence for
liraglutide>semaglutide> exenatide extended release. For SGLT-2
evidence modestly stronger for empagliflozin>canagliflozin.
ASCVD: atherosclerotic cardiovascular disease; CKD: chronic kidney
disease; CV: cardiovascular; CVD: cardiovascular disease; CVOT:
cardiovascular outcome trial; DPP-4: dipeptidyl peptidase-4 inhibitor;
eGFR: estimated glomerular filtration rate; GLP-1: glucagon-like peptide-
1 receptor agonist; HF: heart failure; SGLT-2: sodium glucose co-
transporter-2 inhibitor
novo nordiskView entire presentation