The short-term safety and efficacy of bariatric/metabolic surgery for the initial remission of type 2 diabetes (T2D) in patients with moderate to severe obesity is well established. However, there are no prospective randomized controlled trials (RCTs) that have tested long-term efficacy, durability, and safety of this approach. Moreover, Level-1 evidence regarding the risks and benefits of bariatric/metabolic surgery in patients with diabetes and only mild obesity is limited. In this context, four investigative groups (Cleveland Clinic, Joslin Diabetes Center/Brigham & Women's Hospital Boston, the University of Pittsburgh, and the University of Washington) have completed RCTs that evaluated the short-term (1-3 years) effectiveness of bariatric/metabolic surgery compared to multidisciplinary medical and lifestyle management of T2D and body weight, including among patients who are only mildly obese or merely overweight. Investigators from these four RCTs have now formed the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium. With the support of an NIH U34 planning grant, we have prepared this U01 application to obtain long-term follow-up data from 302 patients with T2D and a BMI of 27-45 kg/m2 (35% with baseline BMI <35 kg/m2), who were randomized to surgical or non-surgical diabetes management approaches. These RCTs include a set of common measures, and all of them have completed and published at least one-year follow-up assessments. Through the U34 mechanism, we merged study participants and harmonized study procedures and outcome metrics into a unified, prospective, longitudinal, observational framework, and to date, we have successfully enrolled 244 participants into a short-term 2 year follow-up. The primary goal of this U01 is to determine long-term (7-year) durability of glycemic control (percentage change in HbA1c from baseline) following random treatment allocation to bariatric surgery or medical/lifestyle intervention. Secondary outcomes include rates of diabetes remission and relapse, efficacy outcomes including fasting plasma glucose, body weight, blood lipids, blood pressure, albuminuria, macro- and microvascular events, cardiometabolic risk score, and quality of life, and safety including hypoglycemia and major cardiovascular events. In exploratory analyses, we will identify clinical predictors of diabetes remission and relapse. Our large, unified cohort will form the first RCT to address these questions, and it represents a cost-effective way to generate essential long-term data. ARMMS-T2D is expected to have high impact because it will provide the largest body of long-term Level-1 evidence to inform decision-making regarding comparative durability, efficacy, and safety of bariatric/metabolic surgery relative to medical/lifestyle management of T2D among patients with mild to moderate obesity.

Public Health Relevance

The short-term safety and efficacy of bariatric surgery for the remission of type 2 diabetes is well established; however, there are no prospective randomized controlled trials that have evaluated the longer-term durability and efficacy. The Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium will provide long-term Level-1, evidence-based data on diabetes remission and related outcomes that will guide clinical practice for patients with diabetes and mild to moderate obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01DK114156-01
Application #
9365554
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Linder, Barbara
Project Start
2017-07-04
Project End
2022-06-30
Budget Start
2017-07-04
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Cummings, David E; Rubino, Francesco (2018) Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia 61:257-264
Kirwan, John P; M├╝nzberg, Heike; Berthoud, Hans-Rudolf (2018) Mechanisms Responsible for Metabolic Improvements of Bariatric Surgeries. Diabetes 67:1043-1044