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Talking Therapeutics

Hot Summer Releases From the ADA

Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS

Volume 5, Issue 1

In the spirit of our prior coverage of the ACC meeting this spring, I'm turning my attention to the latest breaking science from the recent virtual American Diabetes Association Scientific Sessions. Before we dive in, I have to mention the blockbuster news from Boehringer Ingelheim that the EMPEROR-Preserved trial met the primary endpoint and demonstrated significant risk reduction with Jardiance (empagliflozin) for the composite of cardiovascular death or hospitalization for heart failure in adults with heart failure with preserved ejection fraction (HFpEF). This paves the way for empagliflozin to become the first and only effective therapy for patients with HFpEF. The full trial results will be published later at the European Society of Cardiology Conference, so I'll hold off on my full analysis until then. For now, let's talk diabetes!

Point 1 : Efpeglenatide Reduces Adverse Cardiac and Renal Events in Type 2 Diabetes

Efpeglenatide is a novel GLP-1 receptor agonist administered weekly by means of subcutaneous injection, and it has been previously shown to lower glucose levels without causing hypoglycemia. The drug consists of a modified exendin-4 molecule conjugated with an IgG4 Fc fragment.

Researchers of the AMPLITUDE-O study analyzed over 4000 patients and found that efpeglenatide reduced cardiovascular event risk by 27%, and kidney disease progression by 32% compared with placebo for high-risk adults with type 2 diabetes. Notably, this benefit was preserved in the 15% of patients on background SGLT2 inhibitor therapy, suggesting these therapies may be a new powerful combination to combat residual cardiovascular (CV) risk in patients with type 2 diabetes.

Point 2: Sotagliflozin Continues to Shine

The dual SGLT1/SGLT2 inhibitor sotagliflozin has previously demonstrated benefit, however, additional data was just presented at the meeting and simultaneously published in the Annals of Internal Medicine.

In the SOLOIST study, sotagliflozin reduced the risk for cardiovascular death, hospitalization for heart failure (HF), and urgent HF visits by 33% among adults with diabetes and acute decompensated HF with an early benefit observed by one month.

In the SCORED trial, the risk for CV death, hospitalization for HF and urgent HF visits was reduced 26% among adults with diabetes and CKD, with a significant benefit by about three months. Importantly, there were strong signals for benefit in patents with HFpEF as well as among women—a group that has previously suffered with few effective treatments. Discussion around the study results highlight that the addition of SGLT1 inhibition with sotagliflozin may confer additional benefit beyond traditional STLT2 inhibitors, particularly in those with impaired renal function.

Point 3: Tirzepatide Is Coming

Tirzepatide is a novel, once-weekly injectable dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of the GIP and GLP-1 incretins into a single molecule. In the SUPRASS 1, 2, 3, and 5 studies, tirzepatide was superior to placebo, semaglutide, titrated insulin degludec, and titrated insulin glargine, respectively, in reducing A1C and body weight. This drug is poised to be a real breakthrough agent for patients with type 2 diabetes; provided that it can demonstrate favorable effects on cardiovascular and renal endpoints as well.

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