![1. Kalra S. Diabetes Ther 2014;5:355–366; 2. Nauck MA & Meier JJ. Lancet Diabetes Endocrinol 2016;4:963–964; 3. Bonaventrua A et al. J Intern Med 2019. doi: 10.1111/joim.12890. [Epub ahead of print];
4. Drucker DJ. Cell Metab 2016;24:15–30
GLP-1RA and SGLT2 inhibitors. Beneficial metabolic and CV
outcomes with different modes of action.
Increased
glucose
filtration
Increased urinary
glucose excretion
SGLT-2i
Glomeruli Proximal
tubule
Distal
tubule
SGLT-1
Proposed modes of action:
• Fluid reduction
• Haemodynamic effects
• Heart metabolism
Proposed modes of action:
• Anti-atherosclerotic
• Reduced platelet aggregation
• Anti-inflammatory effects
GLP-1RA](https://image.slidesharecdn.com/presentationfinalmontanya-210513173555/85/Presentation-final-montanya-16-320.jpg)
Uploaded bySociedad Española de Cardiología
Presentation final montanya
The document discusses the relationship between diabetes and cardiovascular diseases, highlighting how individuals with type 2 diabetes (T2D) face significantly higher risks for conditions like ischemic stroke and heart failure. It emphasizes the importance of personalized and cardiovascular risk-focused management strategies, including the use of different medication classes such as SGLT-2 inhibitors and GLP-1 receptor agonists. Furthermore, it outlines the complexities of diabetes management in relation to cardiovascular outcomes and the necessity of comprehensive lifestyle changes.
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Presentation final montanya
- 1. Diabetes 2021. Cardiólogos yEndocrinólogos: ¿matrimonio o divorcio? Eduard Montanya
- 2. Disclosures • Speaker, AdvisoryPanel or Research Support: AstraZeneca, Menarini, Merck Sharp & Dohme, Novo Nordisk, Novartis and Sanofi
- 3. Beckman J-A andCreager M-A. Circ Res 2016;118:1771–1785; 2. Dunlay SM et al. Circulation 2019;140:e294–e324. Cardiovascular disease and diabetes Stroke • Increased risk of ischemic stroke • Poorer outcomes following stroke (neurological deterioration, death) Coronary artery disease • Increased risk of MI • Impact of MI worse in people with T2D (CV death, MI, stroke) Heart failure (HF) • 2–4 fold increase in risk of developing HF • Increased risk of morbidity and mortality with established HF Peripheral arterial disease • 2–4 fold increase in risk of developing PAD (ankle–brachial index ≤0.90)
- 4. CVD is theleading cause of death in people with T2D 0 7 40 50 60 70 80 90 Age (years) Years of life lost 6 5 4 3 2 1 0 7 6 5 4 3 2 1 0 Men 40 50 60 70 80 90 0 Age (years) Women Non-vascular deaths Vascular deaths Years of life lost in people with diabetes compared with non-diabetes peers Seshasai et al. N Engl J Med 2011;364:829-41
- 5. Many factors contributeto increased CV risk in T2D Libby P, Plutzky J. Circulation 2002;106:2760–2763. Pancreas Hypertension LDL Genetic predisposition Hyperglycaemia Glycated protein Thrombosis Liver Adipocytes Lipaemia Skeletal muscles Insulin resistance: FFA Hyperglycaemia TNF- Hyper-insulinaemia Advanced glycation end-product Fibrinogen PAI-1 CRP FFA HDL Dyslipidaemia VLDL ( TG) 79% of patients with T2D are overweight or obese 63% of patients with T2D have arterial hypertension 70% of patients with T2D have dyslipidaemia
- 6. Guidelines recommendations havemoved towards a more personalized and CV risk-focused approach 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2018 ADA/EASD consensus Patient stratification by CV risk 1998 European consensus: A focus on obesity and undefined glycemic control 2008 ADA standards of care: Individualized glycemic targets 2013 AACE consensus statement: Patient stratification by baseline HbA1c 1999 European guidelines: A focus on stricter HbA1c targets 2013 ADA/EASD position statement: Focus on HbA1c with no drug class preference
- 7. American Diabetes Association.Diabetes Care 2021;44(Suppl 1):S1–S232. Buse JB, et al. Diabetologia 2020;63:221–228. Lipscombe L, et al. Can J Diabetes 2020;44:575e591. Management of hyperglycemia in T2DM CKD FIRST-LINE therapy is metformin and comprehensive lifestyle (including weight management and physical activity) ASCVD / indicators of high risk Compelling need to minimize weight gain or promote weight loss Compelling need to minimize hypoglycemia Cost is a major issue NO If HbA1c above target proceed as below Indicators of high-risk or established ASCVD, CKD or HF Consider independently of baseline HbA1c, individualized target or metformin use HF
- 8. MET SU TZDDPP-4i GLP-1RA SGLT-2i Insulin (basal) Physiological action(s) ↑ insulin sensitivity ↓ hepatic glucose production ↑ insulin secretion ↑ insulin sensitivity ↑ insulin secretion† ↓ glucagon secretion† ↑ insulin secretion ↓ glucagon secretion Slows gastric emptying ↑ satiety ↑ renal glucose elimination ↑ glucose disposal ↓ hepatic glucose production Efficacy (↓HbA1c) High High High Intermediate High/Very high Intermediate Highest Hypoglycaemia risk Low Moderate Low Low Low Low High Weight effect ↔ ↑ ↑ ↔ ↓ ↓ ↑ Major side effects GI Hypoglycae mia Oedema Heart failure Bone fractures Rare GI Genito- Urinary infection, DKA Hypoglycaemia Hypoglycemic agents
- 9. Incretins and SGLT-2inhibitors Incretin-based therapies DPP-4 inhibitors GLP-1RAs • Stimulate insulin release • Inhibit glucagon release • Reduce blood glucose by inhibiting renal reabsorption Sitagliptin Saxagliptin Linagliptin Alogliptin Vildagliptin Exenatide Liraglutide Lixisenatide Dulaglutide Semaglutide Canagliflozin Dapagliflozin Empagliflozin Ertugliflozin Treatment options SGLT-2 inhibitors
- 10. GLP-1 secretion andGLP-1 receptor expression GLP-1, glucagon-like peptide-1; GLP-1R, glucagon-like peptide-1 receptor Merchenthaler I et al. J Comp Neurol 1999;403:261–280; Baggio LL, Drucker DJ. Gastroenterology 2007;132:2131–2157; Ban K et al. Circulation 2008;117:2340–2350; Vrang N et al. Prog Neurobiol 2010;92:442–462; Pyke C et al. Endocrinology 2014;155:1280–1290 Neurons in hindbrain L-cells of the gut GLP-1 is secreted by: GLP-1R is expressed in: Heart Gastrointestinal tract Brain Kidney Pancreas Lung
- 11. GLP-1RAs have multifactorialeffects GLP-1, glucagon-like peptide-1; GLP-1RA, glucagon-like peptide-1 receptor agonist. Adapted from Campbell JE and Drucker DJ. Cell Metab 2013;17:819–37; Lee and Lee. Ann Pediatr Endocrinol Metab 2017;22:15–26 and Pratley RE and Gilbert M. Rev Diabet Stud 2008;5:73–94. A full reference list for this slide can be found in the slide notes. Liver Brain Pancreas Stomach Cardiovascular risk2 Fatty acid metabolism3 Cardiac function3 Systolic blood pressure3 Inflammation4 Endogenous glucose production10 Hepatic insulin sensitivity10 De novo lipogenesis10 Lipotoxicity10 Steatosis11 Beta-cell function1 Insulin biosynthesis1 Glucose-dependent insulin secretion1 Glucose-dependent glucagon secretion1 Body weight5 Food intake6 Satiety7,8 Gastric emptying9 Cardiovascular
- 12. Proximal tubule Segments S1-S2 SGLT1~10% Glucose reabsorción S3 No glucosuria Adapted from Ferrannini E, et al. Nat Rev Endocrinol. 2012;8(8):495-502 SGLT2i mode of action. Tubular reabsortion of glucose in healthy subjects SGLT2 ~90% glucose reabsortion Glucose
- 13. Proximal tubule Segments S1-S2 SGLT1~10% Glucose reabsorción S3 Glucosuria when blood glucose is above 180 mg/day SGLT2 ~90% glucose reabsortion Gerich JE. Diabet Med. 2010;27:136-42 In type 2 diabetes SGLT-2 are overexpressed and glucose reabsortion is increased and urinary glucose excretion is reduced Glucose Tubular reabsortion of glucose is increased in T2DM
- 14. SGLT-2 Inhibitor SGLT-2 inhibition reduces glucose reabsortionin proximal tubule, resulting in glucosuria, osmotic diuresis and caloric loss Glucosuria ≈ 78 g/day Caloric loss ≈ 312 kcal/day Efficacy is dependent on the amount of glucose filtered, which depends upon plasma glucose levels and glomerular filtration rate. Thus, efficacy declines with progressive renal impairment as glomerular filtration rate declines. SGLT-1 Mode of Action of SGLT2i. Tubular reabsortion of glucose is inhibited SGLT2i
- 15. SGLT-2 Inhibitor SGLT-2 inhibition reduces glucose reabsortionin proximal tubule, resulting in glucosuria, osmotic diuresis and caloric loss Glucosuria ≈ 78 g/day Caloric loss ≈ 312 kcal/day Efficacy is dependent on the amount of glucose filtered, which depends upon plasma glucose levels and glomerular filtration rate. Thus, efficacy declines with progressive renal impairment as glomerular filtration rate declines. SGLT-1 Mode of Action of SGLT2i. Tubular reabsortion of glucose is inhibited SGLT2i
- 16. 1. Kalra S.Diabetes Ther 2014;5:355–366; 2. Nauck MA & Meier JJ. Lancet Diabetes Endocrinol 2016;4:963–964; 3. Bonaventrua A et al. J Intern Med 2019. doi: 10.1111/joim.12890. [Epub ahead of print]; 4. Drucker DJ. Cell Metab 2016;24:15–30 GLP-1RA and SGLT2 inhibitors. Beneficial metabolic and CV outcomes with different modes of action. Increased glucose filtration Increased urinary glucose excretion SGLT-2i Glomeruli Proximal tubule Distal tubule SGLT-1 Proposed modes of action: • Fluid reduction • Haemodynamic effects • Heart metabolism Proposed modes of action: • Anti-atherosclerotic • Reduced platelet aggregation • Anti-inflammatory effects GLP-1RA
- 17. Cardiólogos y Endocrinólogos: ¿matrimonioo divorcio? Una pareja de hecho