Rise Study compared gastric banding to metformin in preserving beta cell functions in people who have prediabetes.
The topic of targeting and treating prediabetes is being looked closer in today’s research. It is well known that beta cells stop secreting insulin due to overexertion from insulin resistance. Studies have shown that by preserving beta cells, we can stop the progression of diabetes, and specifically weight loss in prediabetes can lead to a reduced incidence of diabetes. The Beta Cell Restoration through Fat Mitigation Study studied the impact of weight loss, by gastric banding in patients who have obesity with either recently diagnosed type 2 diabetes or impaired glucose tolerance. The study hypothesized that weight loss from gastric banding would be superior to metformin in preserving and restoring beta cell function, thus reversing diabetes.
There were 88 participants who were randomized 1:1 into either metformin treatment or gastric banding and nutrition management. Although this sample size was small, it was sufficient to detect a 0.6 difference in beta cell function between the two groups. The study included patients with a BMI between 30 and 40, fasting glucose over 90 mg/dL, or oral glucose tolerance test of over 140 mg/dL, and an A1C less than 7.0%. Patients in the gastric band group were seen every two months for the first year, then every three months for the second year, and adjustments were made accordingly. The ANOVA test and Fisher exact test were used to perform statistical analysis.
Researchers used a process known as clamping in the gastric banding group where dextrose levels were held to certain constants over time in order to check the C-peptide response. Patients were injected with dextrose and plasma glucose was raised to over 25 mmol/L to inject 5g of arginine. The glucose, insulin, and c-peptide levels were checked in the plasma before and after the injection, and insulin sensitivity was calculated as a ratio of these measures. There were 70 participants who completed two years of this test. Primary outcomes looked at steady state and acute C-peptide concentrations. This group also received dietary restrictions and healthy lifestyle education. Participants on the metformin treatment were titrated up to the therapeutic range of 2,000 mg/day and started the therapy immediately.
There was a 10.7kg drop in patients who got the gastric band, mostly in the first six months, while the metformin group lost on average only 1.7 kg. The acute C-peptide response to the maximum level of glucose fell significantly by 18% in the metformin group over two years but not in the gastric band group. Insulin sensitivity also increased in both groups. At two years, insulin sensitivity increased 45% and 25% from baseline in the band and metformin group respectively, translating into steady state C-peptide concentrations decreasing 16% and 8% respectively. A1C and fasting plasma glucose fell in both groups but remained lower than baseline at two years significantly in the band group.
This study showed that gastric banding and metformin had similar effects. Insulin sensitivity increased but then diminished, and a decline in C-peptide was seen accordingly. This study did not show an improvement or preservation of beta cells; the therapies given simply decreased the amount of insulin secreted in response to a lower blood glucose level. Safety was also a concern in the gastric band group with 5 out of the 44 participants experiencing serious adverse events. Two participants developed breast cancer within the first 8 months of treatment. As the study progressed, two patients had band slippage and had to have bands removed. The final adverse event was a hospitalization for an inflamed gallbladder. This contrasts with established T2D where these interventions are a protective factor. In this case longer term studies are needed to establish whether there is actually a protective factor in this treatment. Dr. Roy Taylor commented that progression to diabetes is a slow process and that it is understandable why this two-year study could not prove its hypothesis.
- Treating prediabetes increased insulin sensitivity, so the beta cells secreted less insulin, but there was no evidence of beta cell preservation.
- Aside from weight loss, gastric banding showed similar efficacy in blood glucose reduction to metformin but had many serious adverse effects, including band slippage.
- It is believed that in the long run, gastric banding will be superior to metformin, but longer-term studies should be done to prove this.
Gastric Band, Metformin Equally Prevent Diabetes in Short-Term – Medscape – Oct 16, 2018.
Xiang, Anny H., et al. “Impact of Gastric Banding Versus Metformin on β-Cell Function in Adults With Impaired Glucose Tolerance or Mild Type 2 Diabetes.” Diabetes Care, American Diabetes Association, 3 Oct. 2018, doi.org/10.2337/dc18-1662.
Arsalan Hashmi, Pharm. D. Candidate 2019, LECOM School of Pharmacy