A combination of metformin/sitagliptin, insulin glargine, and lifestyle modifications did not cause remission of type 2 diabetes (T2D) in people with the disease after discontinuing previous glucose-lowering medications, according to a study in Diabetes Care.
The open-label, parallel, randomized controlled trial assigned patients with T2D to either a 12-week intervention group treated with sitagliptin/metformin, insulin glargine, and lifestyle modification, or to a control group treated with standard T2D care. The primary outcome was the hazard ratio of relapse throughout the entire study period.
The study defined remission of T2D as any of the following: a capillary glucose level ˃10 mmol/L on ≥50% of measurements over 1 week in the absence of acute illness; glycated hemoglobin (HbA1c) levels ≥6.5%; use of any glucose-lowering medication; fasting plasma glucose ≥7.0 mmol/L; or a 2-hour postprandial plasma glucose ≥11.1 mmol/L during an oral glucose tolerance test. The supplementary definition of relapse was the same but excluded the fasting plasma glucose and the 2-hour postprandial plasma glucose level measurements.
A total of 102 people with T2D were enrolled at 6 Canadian diabetes centers between July 2016 and May 2018. The group was 37% women and were aged mean (SD) 55.5 (9.0) years, with a body mass index of 31.6 (4.7) kg/m2, and had T2D for 24 (16.9) months.
The primary definition of relapse was met by 41 (82%) of participants in the intervention group and 48 (92%) in the control group (hazard ratio [HR] 0.72, 95% CI, 0.47-1.1, P = .13). Nonsignificant differences were observed between the treatment groups at prespecified time points when the same relapse definition was used.
The supplementary definition of T2D remission was met by 37 (74%) participants in the intervention group and 46 (88%) of participants in the control group during the follow-up (HR 0.60, 95% CI, 0.39-0.95, P = .03). Using these criteria, 13 (26%) intervention group participants and 5 (10%) control group participants were in remission at 36 weeks (relative risk [RR] 2.70, 95% CI, 1.04-7.03, P = .04) with no significant differences at other time points.
Study limitations noted by the researchers included overestimation of the intervention effects in their sample size calculation and the inability to blind participants and research staff to the study treatments due to the nature of the intervention.
“Although our overall results were not statistically significant, the data suggest that the tested approach may partially but not completely restore glucose homeostasis,” the investigators commented.
Disclosure: This study was funded by Merck, makers of Janumet®, the brand name of sitagliptin and metformin HCI. Some of the study authors declared affiliations with Merck and other pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
McInnes N, Hall S, Hramiak I, et al. Remission of type 2 diabetes following a short-term intensive intervention with insulin glargine, sitagliptin, and metformin: results of an open-label randomized parallel-design trial. Diabetes Care. Published online November 2, 2021. doi:10.2337/dc21-0278