Piloting a Remission Strategy in Type 2 Diabetes

Results of a Randomized Controlled Trial

Natalia McInnes; Ada Smith; Rose Otto; Jeffrey Vandermey; Zubin Punthakee; Diana Sherifali; Kumar Balasubramanian; Stephanie Hall; Hertzel C. Gerstein


J Clin Endocrinol Metab. 2017;102(5):1596-1605. 

In This Article

Abstract and Introduction


Objective: This trial assessed the feasibility, safety, and potential to induce remission of a short-term intensive metabolic strategy.

Design: A randomized, parallel, open-label pilot trial with 83 participants followed for 52 weeks.

Setting: Ambulatory care.

Participants: Patients with type 2 diabetes of up to 3 years in duration.

Interventions: Participants were randomized to: (1) an 8-week intensive metabolic intervention, (2) a 16-week intensive metabolic intervention, or (3) standard diabetes care. During the intensive intervention period, weight loss and normoglycemia were targeted using lifestyle approaches and treatment with metformin, acarbose, and insulin glargine. Diabetes drugs were then discontinued in the intervention groups and participants were followed for hyperglycemic relapse.

Primary Outcome: On-treatment normoglycemia.

Results: At 8 weeks, 50.0% of the 8-week intervention group vs 3.6% of controls achieved normoglycemia on therapy [relative risk (RR), 14.0; 95% confidence interval (CI), 1.97 to 99.38), and at 16 weeks, these percentages were 70.4% in the 16-week group and 3.6% in controls (RR, 19.7; 95% CI, 2.83 to 137.13). Twelve weeks after completion of the intervention, 21.4% of the 8-week group compared with 10.7% of controls (RR, 2.00; 95% CI, 0.55 to 7.22) and 40.7% of the 16-week group compared with 14.3% of controls (RR, 2.85; 95% CI, 1.03 to 7.87) met hemoglobin A1C criteria for complete or partial diabetes remission.

Conclusions: A short course of intensive lifestyle and drug therapy achieves on-treatment normoglycemia and promotes sustained weight loss. It may also achieve prolonged, drug-free diabetes remission and strongly supports ongoing studies of novel medical regimens targeting remission.


Type 2 diabetes is typically treated using lifestyle approaches and a stepwise addition of oral and injectable medications. Such regimens lose effectiveness with time due to disease progression and difficulty adhering to lifestyle changes and multiple drug combinations. For the patient, this means that a diagnosis of diabetes is the first step on the path of chronic, increasingly complex therapeutic regimens. Recent data suggest that this may not be inevitable and that diabetes may be partially or even completely reversed, at least in some patients. For example, short-term intensive insulin therapy,[1–12] oral diabetes drugs,[9–11] intensive lifestyle therapy,[13–15] a low-carbohydrate Mediterranean diet,[16] or a very-low-calorie diet[17] can reverse diabetes in up to 40% of patients, and bariatric surgery can induce diabetes remission in up to 95% of patients.[18–23] These data highlight the importance of considering and testing alternative treatment paradigms for type 2 diabetes that focus on reversing the disease rather than simply controlling progressive hyperglycemia. They also suggest that achieving normoglycemia on therapy using one or more approaches may be an important component of any remission strategy. We therefore conducted a pilot trial to determine whether a short-term intensive metabolic approach that targeted fasting and postprandial normoglycemia and weight loss using a combination of pharmacological and lifestyle approaches was feasible and safe, and whether it showed the potential to induce sustained diabetes remission.