Episode 114: Diabetes care update

Yvette presents updates from ADA on diabetes care regarding SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone. Written by Yvette Singh, MSIV, American University of the Caribbean. Comments and text edition by Hector Arreaza, MD. 

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The American Diabetes Association (ADA) released revisions in May 2022; specifically regarding sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and finerenone for cardiovascular and renal comorbidities. 

What are SGLT2 inhibitors and GLP-1 receptor agonists?

SGLT2 inhibitor class of oral antidiabetic drugs, including empagliflozin, canagliflozin, dapagliflozin, and more. They increase the excretion of glucose and sodium in the urine by inhibiting SGLT2 in the kidney, thus lowering blood glucose levels. In other words, it has a glucoretic effect. 

GLP-1 receptor agonists are a class of non-insulin drugs, including exenatide, liraglutide, semaglutide, and more. They mimic the intestinal hormone incretin and bind to its receptor, which slows the rate at which foods leave the stomach, controls appetite, and regulates insulin and glucagon secretion.

What is the NEW use of SGLT-2 Inhibitors and GLP-1 RA in treatment?

Traditional glucocentric approaches recommend initial medications such as metformin for most adults with type 2 diabetes, leaving SGLT-2 inhibitors and GLP-1 receptor agonists as alternative options mainly for patients with high risk for atherosclerotic cardiovascular disease in whom additional glucose lowering was needed after metformin treatment. 

Current guidelines now recommend these agents (SGLT-2 inhibitors and GLP-1 RA) for any T2DM patient with current or high-risk for ASCVD, chronic kidney disease (CKD), or heart failure (HF). This guideline stands regardless of the need for additional glucose lowering and/or metformin use. This has now changed through trials, demonstrating that cardiovascular disease and chronic kidney disease benefits independent of a medication’s glucose-lowering potential.

HbA1c has long been used to guide clinical decision-making about type 2 diabetes. However, systematic reviews have revealed minimal benefits in the normalization of HbA1c.

Moreover, the cardiovascular and kidney protection of SGLT-2 inhibitors and GLP-1 receptor agonists are unrelated to their impact on HbA1c. Double-blinded randomized clinical trials showed that SGLT-2 inhibitors reduced the risk of cardiovascular death and hospitalization for heart failure in patients with or without diabetes. Therefore, cardiovascular and kidney risk, rather than HbA1c, constitutes a possible indication for the two medication classes. 

If patients with ASCVD remain above goal A1C despite the addition of an SGLT-2 inhibitor or GLP-1 RA, then adding the agent the patient is not currently on out of the two is recommended before dipeptidyl peptidase-4 aka (DPP-4) inhibitors, basal insulin, or sulfonylureas because the combined use of an SGLT-2 inhibitor and GLP-1 RA can produce an additive risk reduction for cardiovascular and renal adverse events.

What is Finerenone, and how does it help with diabetes? 

Finerenone (Kerendia®) selectively blocks sodium reabsorption and overactivation of mineralocorticoid receptors within epithelial and non-epithelial tissues. This, in turn, reduces fibrosis and inflammation of both the kidneys and blood vasculature.

Finerenone use for patients with advanced CKD, i.e., moderately elevated albuminuria, eGFR of 25- 60 mL/min, and diabetic retinopathy, is encouraged for nephroprotection. However, Patients with less-advanced CKD, i.e., stages 1-2, do not receive any benefit. Regardless of the severity of CKD, SGLT-2 inhibitors remain first-line therapy.

Although Finerenone improves cardiovascular outcomes and reduces CKD progression for patients, it is still unknown if there are any additive cardioprotective effects if used with SGLT2 inhibitors and/or GLP-1 receptor agonists.

Some Closing Pearls: 

The use of SGLT2 inhibitors in patients with eGFR > 25 decreased from 30 previously.

If the A1c goal is not being met, combination therapy of insulin with a GLP receptor agonist can be considered, as this combination treatment has been shown to increase the efficacy and duration of insulin.

Overall, this new change could be very beneficial if accepted internationally. Though understandably, there could be some limitations to this guideline given the availability and cost of these medications, as well as their contraindication of use in specific populations such as pregnancy, ages >65 with concurrent risk factors for hypoglycemia or dehydration, and those with history of acute pancreatitis. 

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Conclusion: Now we conclude our episode number 114 “Diabetes care update.” Yvette explained that the ADA now recommends the use of SGLT2 inhibitors and GLP-1 agonists in any patient with type 2 diabetes with current or at high risk for cardiovascular disease, chronic kidney disease, or heart failure. Primary care physicians should become familiar with the dosing, cautions, side effects, and contraindications of these meds. Also, a newer medication for CKD in diabetes was mentioned: Finerenone. Diabetes treatment continues to evolve, and we hope this information is useful for you. 

This week we thank Hector Arreaza, Yvette Singh, and Fiona Axelsson. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! 

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1. Lacanlale, Jana K et al. “Notable Revisions in Diabetes Treatment According to ADA Guidelines.” Pharmacy Times, 26 Mar. 2021, https://www.pharmacytimes.com/view/notable-revisions-in-diabetes-treatment-according-to-ada-guidelines.
2. Li, Sheyu, et al. “SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.” British Medical Journal 2021; 373:n1091. doi:10.1136/BMJ.n1091
3. Royalty-free music used for this episode: BUrn Flow by Gushito, downloaded on September 22, 2022, from https://www.videvo.net/royalty-free-music-track/burn-flow/1008877/

 

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