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Is Weight Loss the Secret Behind Remission of Type 2 Diabetes?

Feb 3, 2018
 

T2D diagnosed within last 6 years may be able to achieve remission if substantial weight loss is achieved.

Temporary regularization of plasma glucose levels by calorie constraint and weight loss was demonstrated in previous studies. More specifically, a study conducted by Sarah Steven et al., concluded that T2D is potentially reversible, due to 40 percent of their subjects achieving remission of diabetes for a period of 6 months following a substantial loss of body weight. However, it has not been explored yet if weight loss provides long-lasting benefits against T2D, and if primary care succor offers an advantage to subjects who are in the quest to attain healthier body weight. Diabetes Remission Clinical Trial, DiRECT study, sought to answers those questions. Primarily, researchers wanted to establish if a sustained weight loss of 10 to 15 kg as a result of primary care support can lead to a long-term remission of T2D and put an end to a lifelong need for antidiabetic drugs.

DiRECT is cluster-randomized, open-label trial conducted in Scotland, across 49 offices of the primary care providers. Individuals who had been diagnosed with T2D within the last 6 years between the ages of 20 and 65, whose BMI was greater than 27 kg/m2, and who had HbA1c levels above 6.5% were eligible to take part in the study. Uncontrolled T2D with A1c levels above 12%, patients requiring insulin use, poor renal function, and recent weight loss were some of the exclusion criteria listed. PCP offices that agreed to participate in the study were assigned in a 1:1 manner to either a control, or experimental groups. A total of 306 participants were enrolled in the trial, each trial arm composed of 148 subjects. Control group patients were treated according to the best-practice care guidelines, while experimental arm individuals received support to follow a standard protocol for weight management, the Counterweight-Plus program, with the goal to maintain a weight loss of 15 kg or more. All antihyperglycemic and antihypertensive medications were discontinued at the enrollment date in the experimental group; the therapies were re-started as necessary following the standard protocols. During the first 3 months of the study, participants in the experimental arm followed a low-energy diet, with caloric intake of 825 to 853 kcal per day. For the following 2-8 weeks, participants’ calorie intake was increased and physical activity approaches were introduced; Step counting was encouraged with hopes of participants being able to maintain their weight loss. The study regarded the loss of weight of 15 kg or more along with the remission of diabetes as the primary outcome of the study.  Quality of life and blood pressure were among secondary outcomes assessed.  Intention-to-treat principle was employed in analyzing the outcomes.

At the conclusion of 12-months, 24% of experimental arm participants achieved a weight loss of 15 kg, which was not seen in control group. Mean weight loss of 10 kilograms was achieved in the intervention group, while subjects following best-practice guidelines achieved a weight loss of 1 kg. Out of 149 patients, 68 patients, or 46% of subjects in the experimental arm achieved complete diabetes remission, compared to 4% of patients in the control group. The remission was statistically significant, p-value <0.0001. With the respect to HbA1c reduction, experimental group subjects experienced a greater decrease of A1c by -0.85% compared to control, p<0.0001.  Number of antidiabetic drugs being taken in the control group increased throughout the trial, while it was reduced in the experimental group. Out of 148 individuals, only 19 were taking any antihyperglycemic drugs at month 12 in the intervention group. In contrast, 121 out of 148 patients in the control arm were being treated with antidiabetic drugs. Although blood pressure measurements were similar across the groups at the conclusion of the trial, 61% of patients in the control group were receiving either one or two antihypertensive therapies, while only half of those did in the intervention group.  Quality of life was enhanced for those patients who were randomized to the weight loss study arm. On contrary, those individuals treated according to best-practice guidelines had a decreased quality of life at the end of the study.

Significance of weight management and remission of type 2 diabetes is of crucial importance. What once was a disease of an older individual, is now affecting a large number of youth, principally due to high incidence of obesity seen in younger population. By having a way to increase life longevity, which is reduced as a result of T2D, both younger and older individuals can achieve remission by opting for following a healthy lifestyle. We have seen here that as a result of primary care support in weight management, remission of diabetes is possible in about 50% of patients. Results from this trial are promising and may pave a road for a change in how we approach T2D treatment. Larger, multinational, randomized controlled trials are needed to see if this trial’s results will be replicated, prior to implementing changes on guideline levels.

Practice Pearls:

  • 46% of patients who lost at least 10 kg of weight achieved remission of diabetes.
  • Individuals who treated their T2D by following a weight management strategy had lower A1c levels by -0.85% compared to individuals who were taking antidiabetic medications.
  • At 12-month follow-up, 74% of patients in weight management group and 18% patients in the control group did not need antihyperglycemic agents to control their type 2 diabetes.

References:

Michael Ej Lean, Wilma Leslie, Alison Barnes, et al. “Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomized trial.” The Lancet. Dec 2017.  http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)33102-1.pdf.  Accessed Jan 2018.

Sarah Steven, Kieren Hollingsworth, Ahman Al-Mrabeh, et al. “Very-Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiologic Changes in Responders and Nonresponders.” Diabetes Care, American Diabetes Association. Mar 2016.  http://care.diabetesjournals.org/content/early/2016/02/24/dc15-1942. Accessed Jan 2018.

Lamija Zimic, PharmD(c), University of South Florida, College of Pharmacy