medwireNews: Continuation of sitagliptin during initiation of insulin glargine therapy results in a greater reduction in glycated hemoglobin (HbA1c), without increased hypoglycemia, than discontinuation in patients with type 2 diabetes, study data show.
“The greater proportion of participants achieving an HbA1c target of <7.0% [<53 mmol/mol] and the greater proportion of participants achieving target HbA1c without hypoglycemia episodes in the sitagliptin group provide additional data to demonstrate the clinically meaningful glycemic benefits of continuing sitagliptin in this setting,” Ira Grantz (Merck & Co., Inc., Kenilworth, New Jersey, USA) and colleagues remark.
The CompoSIT-I (comparison of sitagliptin vs placebo during initiation of insulin) trial included 743 patients (mean age 58 years) from 22 countries who had inadequately controlled type 2 diabetes on metformin (≥1500 mg/day) in combination with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and/or a sulfonylurea.
Patients not taking sitagliptin at enrolment were switched to this drug and stabilized during a run-in period, following which all patients were randomly assigned to continue sitagliptin (n=373) or to discontinue and receive a matched placebo instead (n=370). At this point, both groups initiated insulin glargine and were instructed to titrate to a target fasting plasma glucose (FPG) level of 4.0–5.6 mmol/L.
At baseline, mean HbA1c was 8.8% (72.5–72.7 mmol/mol) in both groups. By week 30, it was 6.9% (51.4 mmol/mol) in the sitagliptin group and 7.3% (56.4 mmol/mol) in the placebo group.
The corresponding mean fall from baseline of 1.9% (20.5 mmol/mol) in the sitagliptin group was significantly greater than the 1.4% (15.5 mmol/mol) reduction observed in the placebo group.
The proportion of participants with HbA1c below 7.0% was significantly higher in the sitagliptin versus placebo group (54.2 vs 35.4%), whereas the mean daily insulin dose (53 vs 61 units) and mean FPG (6.5 vs 6.8 mmol/L) were significantly lower.
And although mean HbA1c was lower with sitagliptin than with placebo, there was no increase in hypoglycemia. In fact the rate of documented symptomatic hypoglycemia with blood glucose at or below 3.9 mmol/L was significantly lower in the sitagliptin group than in the placebo group, at 1.6 versus 2.1 events per person–year.
The proportion of individuals who reached the HbA1c target of less than 7.0% without experiencing hypoglycemia was also higher with sitagliptin (15.3%) than with placebo (10.0%).
In addition, the researchers note that the adverse event rate was similar between the two groups and there was no clinically meaningful difference in the change in body weight from baseline (1.5 vs 1.7 kg for sitagliptin vs placebo).
Writing in Diabetes, Obesity & Metabolism, Grantz and co-authors conclude that they believe their findings will “be useful to clinicians making individualized patient decisions about intensification of treatment for patients with type 2 diabetes when initiating basal insulin therapy.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group