Going Gaga for GLP-1 Agonists

Volume 12, Issue 4

SGLT2 inhibitors have garnered tremendous excitement as novel agents to reduce the risk of cardiovascular disease in patients with diabetes. The accolades are deserving, as these agents boast a robust amount of data demonstrating lower risks for major adverse cardiac events (MACE).

Conversely, the GLP-1 agonists have not received quite as much attention and fanfare despite having similarly positive data. This could be due to the nonoral route of administration for most GLP-1 agonists, or it could simply reflect a weaker marketing campaign. In this week’s issue of Talking Therapeutics, we shed the spotlight on new GLP-1 agonist data.

Point #1: GLP1 Agonists Play Nicely With SGLT2 Inhibitors

While both the GLP-1 agonists and the SGLT2 inhibitors can reduce the risk of MACE when given as monotherapy to patients with diabetes, data on combining them is generally lacking.

New data from the AMPLITUDE-O trial, demonstrates the effect of efpeglenatide on cardiovascular outcomes and compared the effects of a GLP-1 agonist efpeglenatide on MACE according to background use of SGLT2 inhibitors. This trial showed that the effect of efpeglenatide vs placebo on MACE and key renal endpoints and did not differ by baseline SGLT2 inhibitor use (P > 0.2). Likewise, the reduction in blood pressure, body weight, low-density lipoprotein cholesterol, and urinary albumin-to-creatinine ratio by efpeglenatide also appeared to be independent of concurrent SGLT2 inhibitor use (P ≥ .08).

Taken together, the results of this trial suggest that the cardiovascular and renal benefits of these two agents can be additive if given in combination with each other.

Point #2: GLP-1 Agonists Help the Kidneys Too

The most recent exciting news with the SGLT2 inhibitors has come in the chronic kidney disease (CKD) arena, as dapagliflozin was recently approved by the FDA for patients with CKD, regardless of the presence of diabetes.

Pooled analysis from the SUSTAIN 6 and LEADER trials were published in Circulation this week, outlining effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes. This new analysis assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline.

In the pooled analysis, semaglutide and liraglutide lowered albuminuria from baseline to 2 years after randomization by 24% vs placebo (95% CI, 20%-27%; P < .001). Both drugs also slowed eGFR slope decline vs placebo. These effects appeared larger in patients with baseline CKD. Semaglutide/liraglutide also significantly lowered risk of persistent 40% and 50% eGFR reductions vs placebo.