Remission of Type 2 Diabetes Following a Short-term Intervention With Insulin Glargine, Metformin, and Dapagliflozin

Abstract

Objective To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches. Methods We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care. At 12 weeks, diabetes medications were discontinued in participants with hemoglobin A1c (HbA1C) < 7.3% (56 mmol/mol). Participants were then followed for diabetes relapse until 64 weeks. The primary outcome was complete or partial diabetes remission (HbA1C < 6.5% [48 mmol/mol] off chronic diabetes drugs) at 24 weeks. Main secondary outcomes were complete or partial diabetes remission at 36, 48, and 64 weeks. Results The primary outcome was achieved in 19 (24.7%) intervention group participants and 13 (16.9%) control group participants at 24 weeks (relative risk [RR] 1.5; 95% confidence interval [CI], 0.8-2.7). The relative risks of remission at 36, 48, and 64 weeks were 2.4 (95% CI, 1.2-5.0), 2.1 (95% CI, 1.0-4.4), and 1.8 (95% CI, 0.7-4.7), respectively. In an exploratory analysis, the intervention reduced the hazard of diabetes relapse with overt hyperglycemia by 43% (hazard ratio 0.57; 95% CI, 0.39-0.81). Conclusions Our primary outcome of diabetes remission at 24 weeks was not statistically significantly different. However, our overall results suggest that some patients with early type 2 diabetes are able to achieve sustained diabetes remission following a short-term intensive intervention. Further studies are needed to optimize the combined therapeutic approach used.

Short‐term intensive insulin as induction and maintenance therapy for the preservation of beta‐cell function in early type 2 diabetes (RESET‐IT Main): A 2‐year randomized controlled trial

“…4,5 There is currently considerable interest in strategies that aim to achieve remission or regression of diabetes through early intervention with intensive lifestyle modification or pharmacotherapy. [6][7][8][9][10][11] The pathophysiological basis of this approach lies in the existence of a reversible component to beta-cell dysfunction that is evident early in the course of T2D (but may not be present later in the natural history). 12 However, this strategy holds both promise and potential limitations, as illustrated by the example of short-term intensive insulin therapy (IIT).…”

Type 2 Diabetes Remission with Significant Weight Loss: Definition and Evidence-Based Interventions

“… 71 In the DiRECT study, to maintain the lost weight, the authors changed participants’ meal patterns variously. 72 In the case of pharmacotherapy, some patients with early diabetes were able to achieve remission after short-term intensive medical therapy, 73 but limited in incretin therapies. There is no study yet on whether remission is maintained after withdrawal of the drug; therefore, lifetime therapy may be required to maintain weight loss.…”

Not Control but Conquest: Strategies for the Remission of Type 2 Diabetes Mellitus

“…However, it has been consistently reported that more than half of patients can achieve remission with recent treatment methods that induce active glycemic control and significant weight loss ( Tables 2 - 4 ). New diabetes drugs with significant weight loss effects have recently been developed and are expected to help patients achieve remission of T2DM [ 23 , 24 ].…”

“…This class of drugs can reduce weight and visceral fat because it is associated with urinary glucose excretion that causes caloric loss [ 86 ]. In a clinical trial using SGLT2 inhibitors in addition to basal insulin and metformin as an intensive intervention, the intervention group with SGLT2 inhibitors achieved more remission than compared to the conventional group (24.7% vs. 16.9%), and reduced the risk of diabetes recurrence by 43% [ 23 ].…”