Short-Term Remission of Type 2 Diabetes With Drug and Lifestyle

About a third of patients with type 2 diabetes may be able to enjoy several months of drug-free remission if they stick to a short course of intensive lifestyle and drug therapy that reduces weight and controls blood glucose, say researchers.

Results from a pilot trial show that 12 weeks after stopping diabetes medications, 11 out of 27 patients (40.7%) with type 2 diabetes who received 4 months of a ramped-up metabolic regimen met HbA_1c criteria for complete or partial diabetes remission, compared with four out of 28 controls (14.3%) who continued to receive standard diabetes care.

Nineteen patients (70.4%) in the 16-week intensive regimen group achieved normoglycemia compared with one control patient (3.6%) 4 months after randomization, reports the research team, led by Natalia McInnes, MD, of McMaster University in Hamilton, Ontario.

"This randomized controlled pilot trial showed that a short-term, intensive metabolic intervention targeting fasting, postprandial normoglycemia, and weight loss was feasible, safe, and capable of achieving normoglycemia in more than 50% of patients and inducing ≥5% weight loss in more than 35% of patients with recently diagnosed type 2 diabetes," Dr McInnes and colleagues say in their report published online March 15 in the Journal of Clinical Endocrinology and Metabolism.

These findings challenge current thinking that type 2 diabetes is "a permanent and progressive disease," they add, noting the results suggest a combination of lifestyle and drug interventions — and not just bariatric surgery — can offer at least short-term disease remission.

"This trial clearly shows that a multifaceted intensive metabolic strategy that targets normoglycemia and weight loss using pharmacological and lifestyle approaches may achieve remission, is acceptable to patients, and may be easily translated into clinical practice," they assert.

Idea of Reversing Diabetes Is "Very Appealing"

And at 52 weeks — 44 weeks after completion of the intervention — four intervention participants (14.3%) and two control participants (7.1%) maintained complete diabetes remission based on the HbA_1c criteria.

In a press release issued by the Endocrine Society, Dr McInnes suggests that shifting the diabetes treatment paradigm from simply controlling blood glucose to inducing remission and then monitoring for relapse could motivate a lot of patients to follow doctors' orders.

"The idea of reversing the disease is very appealing to individuals with diabetes," she says.

For the parallel, open-label pilot study, which was conducted between February 11, 2011 and January 9, 2014, 83 patients with type 2 diabetes of up to 3 years' duration were randomized to one of three treatment groups: an 8-week intensive intervention; an identical intervention over a period of 16 weeks; or standard diabetes therapy. All participants were between 30 and 80 years of age and had a body mass index (BMI) of 23 kg/m² or greater.

Those randomized to standard care received usual glucose management from their regular healthcare provider as well as conventional lifestyle advice and a pedometer.

Participants in the intensive-intervention groups received an exercise plan for achieving and maintaining 150 minutes per week of moderate-intensity physical activity and a meal plan that cut their energy intake by 500 to 750 calories a day to try to generate a sustained weight reduction of 5% or more.

They also received metformin, acarbose, and insulin glargine (Lantus, Sanofi) to help achieve and maintain a fasting capillary glucose of 4.0 to 5.3 mmol/L by week 4.

After oral diabetes medications and insulin were discontinued in the intervention patients, a follow-up schedule reinforced lifestyle changes, regular glucose monitoring, and treatment with metformin and acarbose.

Commenting on the choice of medication used in this pilot study, senior investigator on the trial, Hertzel C Gerstein, MD, MSc, FRCPC, also of McMaster University and Hamilton Health Sciences, said: "We chose to use metformin, acarbose, and basal insulin glargine…as these medications have all been shown to slow or prevent the development of type 2 diabetes.

"However, other drug combinations could lead to higher remission rates and need to be systematically studied with regard to this outcome," he commented in the press release.

And the findings indicate that an 8-week course of intensive metabolic therapy may not be sufficient for inducing remission, and "an induction therapy of a longer duration might be needed," the researchers conclude.

This study was funded by the Canadian Diabetes Association and Population Health Research Institute. Dr McInnes reports financial relationships with AstraZeneca, Merck, and Sanofi. Dr Gerstein has received grant support from Sanofi, Lilly, AstraZeneca, and Merck; honoraria for speaking from Sanofi, Novo Nordisk, AstraZeneca, and Berlin Chemie; and consulting fees from Sanofi, Lilly, AstraZeneca, Merck, Novo Nordisk, Abbot, Amgen, Boehringer Ingelheim, and Kaneq Bioscience. Disclosures for the coauthors are listed in the paper.

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J Clin Endocrinol Metab. Published online March 15, 2017. Abstract

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