Real-World Insulin Deintensification and Discontinuation with GLP-1 Incretin Therapies Versus SGLT2 Inhibitors in Type 2 Diabetes

Semaglutide is associated with a higher rate of basal insulin discontinuation compared to SGLT2 inhibitors, while tirzepatide shows greater insulin dose reduction and glycemic improvement.

Summary and findings

This study analyzed the impact of semaglutide and other GLP-1 receptor agonists on insulin deintensification in type 2 diabetes patients already on basal insulin. The findings indicated that 27.8% of patients on semaglutide discontinued basal insulin compared to 22.2% on SGLT2 inhibitors. Additionally, semaglutide was associated with a significant reduction in basal insulin dose by ≥20% compared to SGLT2 inhibitors.

Abstract

In type 2 diabetes, adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal insulin can improve glycemic control and reduce insulin requirements while counteracting insulin-associated weight gain. However, the extent to which incretin therapies enable patients to stop or meaningfully reduce insulin, and whether they differ in this respect from other oral antidiabetic agents, remains uncertain. Here we analyzed de-identified electronic health records from a federated U.S. clinical network, comparing patients with type 2 diabetes receiving basal insulin who initiated semaglutide, tirzepatide, or an SGLT2-inhibitor (SGLT2-i). Three comparisons were evaluated using 1:1 propensity-score matching: two incretin-versus-SGLT2-i comparisons, semaglutide versus SGLT2-i (n=1,029) and tirzepatide versus SGLT2-i (n=254), and a head-to-head incretin comparison of tirzepatide versus semaglutide (n=272). Cumulative incidence of basal insulin discontinuation and of ≥20% basal-dose reduction was estimated over 24 months. At 24 months, patients who initiated semaglutide discontinued basal insulin at a significantly higher rate than those who initiated SGLT2-i (27.8% vs 22.2%; subdistribution hazard ratio [sHR] 1.26, 95% CI 1.05–1.52; Gray P=0.013), whereas tirzepatide initiators discontinued more often than SGLT2-i initiators without reaching significance (38.4% vs 31.5%; sHR 1.22, 95% CI 0.86–1.71; P=0.263). In the head-to-head incretin comparison, tirzepatide initiators discontinued basal insulin more often than semaglutide initiators, though this difference did not reach significance (38.0% vs 28.5%; sHR 1.35, 95% CI 0.97–1.89; P=0.080). Reduction of basal insulin dose by ≥20% was significantly higher with each incretin than with SGLT2-i (semaglutide sHR 1.15, P=0.045; tirzepatide sHR 1.40, P=0.015), and, in the head-to-head incretin comparison, significantly higher with tirzepatide than semaglutide (sHR 1.29, P=0.045). These reductions in insulin use were accompanied by improved glycemic control. At 6 months HbA1c dropped 1.16 versus 0.92 percentage points for semaglutide versus SGLT2-i (P=0.013), and tirzepatide lowered HbA1c more than SGLT2-i (1.79 vs 1.44 percentage points), though not significantly (P=0.18); in the head-to-head incretin comparison, tirzepatide lowered HbA1c more than semaglutide (1.85 vs 1.30 percentage points; P=0.008). In summary, in a real-world type 2 diabetes population receiving basal insulin, incretin therapies were associated with higher rates of basal-insulin dose reduction than SGLT2-i—and semaglutide with higher rates of discontinuation—while tirzepatide produced greater dose reduction and glycemic improvement than semaglutide, motivating prospective evaluation of incretin-based insulin de-escalation strategies.

Elsewhere in the Semaglutide corpus