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SGLT2 Inhibitors and GLP1 Agonists
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The world of diabetes management has changed dramatically in the past several years. Given the new ADA guidelines and all the new literature on SGLT2 inhibitors and GLP1 receptor antagonists, endocrinologist Dr. Beth Lamos is back to help us understand how to use these drugs in practice.
- SGLT-2 inhibitors and GLP-1 agonists are gaining more traction as second-line agents after metformin given the increase in data suggesting their beneficial effects on not just weight loss and A1c reduction, but also renal and CV protection.
- GLP-1 agonists may be beneficial for patients who want to have a once weekly injection.
- SGLT-2 inhibitors (-flozins):
- Blocks the SGLT-2 receptor in the kidney allowing glucose to be lost in the urine
- A1c reduction 0.5-1%
- May lead to weight loss
- May reduce blood pressure
- Renal protection
- Some have been shown to reduce MACE outcomes
- Renal insufficiency, particularly in those with some baseline renal dysfunction
- Contraindicated if GFR < 30
- Diabetic ketoacidosis that can happen at normal glucose levels with the following risk factors:
- Surgical stress
- Alcohol use
- Reduction in insulin with food intake
- Orthostatic hypotension
- Potential increase in fungal infections
- Rare but serious genital infections including gangrene
- Increased risk of amputation with canagliflozin for people with peripheral vascular disease or severe peripheral neuropathy
- EMPA-REG (empagliflozin)
- Showed reduction in MACE outcomes
- CANVAS (canagliflozin)
- Showed reduction in hospitalization and heart failure
- DECLARE (dapagliflozin)
- Mixed but did not show increase in CV risk
- GLP-1 agonists (-tide):
- Stimulate incretin to make us feel fuller faster, tel the brain we are not hungry and regulate insulin/glucagon from the pancreas
- Weight loss
- A1c reduction
- May be once a week injection (semaglutide and dulaglutide)
- Reduction of CV disease (semaglutide and dulaglutide)
- Likely improvement in renal function
- GI side effect in 30-40% of people: nausea and diarrhea that generally subsides with time
- Should not be used for someone with history of gastroparesis
- Semaglutide (signal for retinopathy risk)
- Contraindicated in those with medullary thyroid cancer or family history of MEN2A or 2B
- Small increase in pancreatitis risk
- LEADER (liraglutide)
- SUSTAIN (semaglutide)
- American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S73-S85. doi: 10.2337/dc18-S008. Review. PubMed PMID: 29222379.
- Gerstein HC, Colhoun HM, Dagenais GR, et al for the REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-130. doi:10.1016/S0140-6736(19)31149-3. Epub 2019 Jun 9. PubMed PMID: 31189511.
- Marso SP, Daniels GH, Brown-Frandsen K, et al for the LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13. PubMed PMID: 27295427; PubMed Central PMCID: PMC4985288.
- Neal B, Perkovic V, Mahaffey KW, et al for the CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PubMed PMID: 28605608.
- Perkovic V, Jardine MJ, Neal B, et al for the CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14. PubMed PMID: 30990260.
- Wanner C, Inzucchi SE, Lachin JM, et al for the EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14. PubMed PMID: 27299675.