The data obtained in the Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) to determine the long-term durability of glycemic control and safety of metabolic/bariatric surgery (MBS) compared with medical/lifestyle management of Type 2 diabetes (T2D) are the largest cohort of randomized patients to date. Over seven years, 355 people with T2D were randomized to MBS versus medical/lifestyle intervention, and 262 (86%) of 305 eligible participants with a range of BMI enrolled in the present study that had a median follow-up of 11 years (range: 7–15 years). Importantly, there was a 25% crossover to MBS, but intention-to-treat analysis was still utilized to address the primary outcome. At seven years, there was more weight reduction in the MBS group (19.9 versus 8.3%, p<0.001), and the reduction in HbA1c was 1.6% for MBS and 0.2% for the medical/lifestyle group (difference: -1.4%, p<0.001).
This benefit ensued despite the use of fewer-anti-diabetes medications. Moreover, diabetes remission was greater after MBS vs. medical/lifestyle (18.2% vs. 6.2%, p=0.02). Importantly, anemia, fractures, and gastrointestinal events were more common after MBS. In summary, at 7 to 12 years follow up, MBS led to superior glycemic control than medical/lifestyle intervention, with less medication usage and higher rates of diabetes remission, including among individuals with lesser degrees of obesity (BMI <35 kg/m2).
There are many strengths to this study. ARMMS-T2D was prospective and NIDDK funded with four cohorts from different centers included. The T2D participants exhibited a range of BMI, often below levels, wherein surgery would be considered and/or reimbursed. A multiplicity of obesity/T2D comorbid outcomes were analyzed. Although most subjects were female, the study had more than one quarter of subjects who were non-white. The intention-to-treat analysis, the gold standard for clinical trials, addressed the relatively high rate of crossover or dropout.
Limitations were also present. As with other MBS trials, the design was open-label. There were differences in the parent trial study in the various centers and lack of uniform baseline and follow-up data from all sites. The design was insufficiently powered to examine the risk of major adverse cardiovascular and microvascular events, cancer, and mortality endpoints. Nor was there sufficient power to determine the relative benefit of the three MBS surgical procedures on outcomes other than weight reduction, wherein adjustable gastric banding proved inferior.
One important issue for any MBS or medical/lifestyle intervention for T2D is the duration of diabetes before randomization. In ARMMS-T2D, the mean duration was eight years, with a range of 4-12 years, with a baseline HbA1c of 8.5%. The natural history of T2D is a progressive decline in glucose-dependent insulin secretion. Note that is at baseline, less than 5% of subjects were on no anti-diabetes medications, and up to 50% were on insulin in addition to oral medications. Thus, this combined cohort had duration of diabetes that was less predictive of benefit from any surgical or medical/lifestyle approach to remission.
Another important dilemma is in defining remission of T2D as an HbA1c of <6.5% on no anti-diabetes mediations. Using this definition, only 18% of the MBS subjects remained free of T2D for seven years. It would not only be interesting to determine glucose tolerance in these subjects but in those whose HbA1c range after randomization was between 5.7-6.5% (prediabetes). Although the median time to crossover from medical/lifestyle to the MBS arm was 4.5 years (range 0.4-9.8), the effect of this interval range on outcome would also be nice to evaluate.
What questions would you appreciate hearing at your presentation?
- How do the results of ARMMS-T2D influence your decision if/when to refer T2D patients for MBS vs. medical/lifestyle to manage their T2D?
- What demographic factors will you use to make the best choice for individual patients with T2D?
- Remission of T2D is defined for patients who are on no anti-diabetes medications by an HbA1c of <6.5% at 6 months, do you agree with this definition?
Dr. Eckel has sat on following consulting/advisory boards: Amarin, Amgen, Arrowhead, Better Co., 89bio, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Co., Tolmar, UpToDate, and Weight Watchers,
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