SURPASS-5: Glycemic, weight benefits of tirzepatide in insulin-dependent type 2 diabetes
medwireNews: People with insulin-dependent type 2 diabetes significantly improve their glycemic control, lose weight, and require less insulin if they also have a weekly injection of tirzepatide, show the SURPASS-5 findings.
The improvements in glycated hemoglobin (HbA1c) were “robust and clinically meaningful,” said Dominik Dahl (Gemeinschaftspraxis für Innere Medizin und Diabetologie, Hamburg, Germany), who presented the findings in a late-breaking poster session at the virtual ADA 81st Scientific Sessions.
The 475 people recruited to the trial were an average age of approximately 60 years, had type 2 diabetes lasting around 13 years, and were on a stable dose of insulin glargine but required a dose increase to achieve glycemic control.
During 40 weeks of follow-up, people randomly assigned to take placebo in addition to insulin achieved an average 0.93 percentage point reduction in HbA1c, from a baseline of 8.37% (68 mmol/mol). However, this necessitated an average 75.0% increase in their daily insulin dose, and they gained an average of 1.7 kg.
By contrast, people randomly assigned to take tirzepatide – a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide (GLP)-1 receptor agonist – achieved HbA1c reductions averaging 2.23, 2.59, and 2.59 percentage points with the 5, 10, and 15 mg/week doses, respectively. Average baseline HbA1c in the tirzepatide arms was 8.23–8.36% (66–68 mmol/mol).
Their insulin needs increased by an average of just 13.0% and 8.1% with the 5 and 10 mg/week doses, respectively, and decreased by 11.4% with the 15 mg/week dose. Moreover, their bodyweight fell by an average of 6.2, 8.2, and 10.9 kg with the three doses, respectively.
Decreased appetite was observed in approximately 7% to 14% of participants taking tirzepatide, compared with 1.7% of the placebo group, potentially contributing to weight loss.
The vast majority (93–97%) of participants in the tirzepatide groups achieved HbA1c levels lower than 7.0% (53 mmol/mol), compared with 34% of the placebo group, and 26–62% versus 3% achieved HbA1c with the nondiabetic range, below 5.7% (39 mmol/mol). Hypoglycemic events occurred at similar rates in all groups, including severe events.
Gastrointestinal events were the most common side effects, in line with the established safety profile of GLP-1 receptor agonists. But these predominantly occurred during the dose-escalation period, which lasted up to 20 weeks depending on the dose, and were infrequent during the rest of follow-up.
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