Focusing Primary Efforts on the Right Interventions in Management of Type 2 Diabetes
Eli Eggen, PharmD, West Side Community Health Services
Background: Type 2 Diabetes Mellitus (T2DM) is a complex and comorbid disease affecting an estimated 27 million people in the United States. In 2015, diabetes was the seventh leading cause of death in the country, with an estimated $245 billion in annual total direct and indirect costs. Current guidelines for treating and managing T2DM encourage targeting lifestyle interventions as first-line efforts to achieve glycemic control. Despite these recommendations, there is arguably more emphasis on pharmacological therapies and using multiple drug treatments to lower blood glucose and reduce cardiovascular risks associated with the disease.
Pathophysiological research has demonstrated a strong association between T2DM and adult weight gain, specifically linking the disease to the buildup of excess fat within the liver and pancreas. Investigators have discovered that calorie restriction in T2DM can normalize fat content in these organs while restoring liver insulin sensitivity. Studies in newly diagnosed T2DM have also provided evidence that normal glucose control can be achieved through weight loss alone, but until this past year, no trial examining the effects of dietary changes has ever assessed sustained disease remission as a primary outcome.
Evidence: A recent study in the United Kingdom investigated whether intensive weight management in a primary care setting could achieve remission of T2DM. The open-label, intention-to-treat, cluster-randomized trial (DiRECT) recruited 306 patients with T2DM from 49 primary care practices located in Scotland and surrounding regions. Patients were 20-65 years of age with a BMI of 27-45 kg/m2, diagnosed with T2DM in the past six years and were not using insulin. Practices were randomized 1:1, providing patients with either a weight management program (intervention) or best-practice care with current guidelines (control) and followed for 12 months. The intervention group underwent withdrawal of all antidiabetic and antihypertensive drugs, and then followed a calorie-restricted diet protocol. Co-primary outcomes were weight loss ≥15 kg and remission of diabetes, defined as achieving a glycated hemoglobin (HbA1c) <6.5% after two months without antidiabetic medications.
There were 149 participants in each group at the end of the study. In the intervention group, 36 participants recorded weight loss of ≥15 kg (none in control group, P<0.0001) with a mean decrease in body weight of 10 kg compared to 1 kg in the control group (adjusted difference -8.8 kg [95% CI -10.3--7.3; P<0.0001]). There were 68 individuals who achieved disease remission in the intervention group while six met the outcome in the control group, OR 19.7 [95% CI 7.8-49.8; P<0.0001]. Remission of diabetes appeared to correlate with the degree of sustained weight loss in the study population. No serious adverse events led to withdrawal from the study.
Discussion: Results from DiRECT demonstrate the significance of reinforcing appropriate lifestyle changes in patients with T2DM. These findings bring attention to the importance of early detection and prevention of T2DM, highlighting the impact weight loss can have on metabolic pathways and possible remission if successful interventions are made in the early stages of diabetes. The study is limited by a small sample size and homogenous patient population (98% white ethnicity, 59% males). Additionally, those included in the trial had only slightly elevated HbA1c at baseline despite inclusion criteria of HbA1c <12.0% (mean HbA1c of 7.7% and 7.5% in the intervention and control groups, respectively). Therefore, it is difficult to apply these conclusions to newly diagnosed patients presenting with a significantly higher HbA1c who previously never sought regular medical care. Further investigation is needed to see if there are similar effects in those with longer disease duration and a higher degree of uncontrolled blood glucose. Additionally, studies of longer duration will help determine if these outcomes can be maintained long term. There is also potential for bias in the trial design due to the nature of the studied intervention, which required all study participants to be unblinded.
Clinical Impact: Primary care practitioners are often required to dedicate considerable direct patient care time attempting to resolve adherence issues, medication side effects, and financial barriers to pharmacological therapies, rather than focusing on supportive lifestyle coaching and developing patients’ self-management skills. The observations in DiRECT should encourage clinicians in primary care settings to continue focusing on lifestyle modifications in T2DM in order to achieve desired outcomes. Although the diagnosis is often overwhelming, patients with new onset T2DM can feel empowered by these promising findings while those opposed to medication therapies may be further motivated to make meaningful lifestyle changes to improve their health.
Centers for Disease Control and Prevention. National diabetes statistics report, 2017: estimates of diabetes and its burden in the United States.https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Published July 18, 2017. Accessed February 16, 2018.
Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. [published online Dec 5, 2017]. Lancet. doi:10.1016/S0140-6736(17):33102-1.
van Eikenhorst L, Taxis K, van Dijk L, de Gier H. Pharmacist-led self-management interventions to improve diabetes outcomes. A systematic literature review and meta-analysis. [published online Dec 14, 2017]. Front Pharmacol. doi:10.3389/fpharm.2017.00891.