Sponsored by:

Trial Summary STAMPEDE

Title: Surgical Treatment and Medications Potentially Eradicate Diabetes Effectively
Trial Sponsor: Ethicon Endo-Surgery with support from LifeScan Inc., and NIH-NIDDK
Year Presented: 2012, 2014
Year Published: 2012, 2014
Topic(s): Prevention/Vascular, General Cardiology, CardioMetabolic
Summary Posted: 03/31/2014
Writer: Dharam J. Kumbhani, MD, SM, F.A.C.C.
Author Disclosure:   CONSULTING FEES/HONORARIA: American College of Cardiology(SIGNIFICANT)
Reviewer: Christopher P. Cannon, MD, F.A.C.C.
Reviewer Disclosure: CONSULTING FEES/HONORARIA: Alnylam(NONE), BMS(NONE), Pfizer (NONE), Lipimedix(NONE), BMS(MODEST), Essentialis(MODEST) OWNERSHIP/PARTNERSHIP/PRINCIPAL: Automedics Medical Systems(NONE) RESEARCH/RESEARCH GRANTS: Accumetrics(MODEST), Boehringer-Ingelheim(SIGNIFICANT), CSL Behring(MODEST), Essentialis(MODEST), Merck(SIGNIFICANT), AstraZeneca(SIGNIFICANT), GSK(SIGNIFICANT), Regeneron/Sanofi(MODEST), Takeda(SIGNIFICANT), Boehringer-Ingelheim(SIGNIFICANT)

Description:

Obesity and type 2 diabetes mellitus (DM) are frequently associated with each other. Although observational studies indicate that glycemic control of type 2 DM improves following bariatric surgery in obese diabetic patients, randomized data are lacking. The current trial sought to compare intensive medical therapy to bariatric surgery in patients with type 2 DM who were either obese or overweight.

Hypothesis:

Bariatric surgery would be superior to intensive medical therapy in improving glycemic control in patients with type 2 DM who were either obese or overweight.

Drugs/Procedures Used:

Eligible patients were randomized in 1:1:1 fashion to either intensive medical therapy alone, intensive medical therapy + Roux-en-Y gastric bypass, or intensive medical therapy + sleeve gastrectomy. All patients received intensive medical therapy as defined by the American Diabetes Association (including lifestyle counseling, frequent home glucose monitoring). Use of newer diabetic medications was permitted. The goal was to achieve a glycated hemoglobin (HbA1c) of ≤6%, or intolerance to medication. All bariatric procedures were performed by a single surgeon, as per standard operating techniques.

Concomitant Medications:

Antihypertensive medications (74%), lipid-lowering medications (83%). Patients undergoing bariatric surgery received vitamin, iron, and calcium supplementation.

Principal Findings:

A total of 150 patients were randomized. However, eight patients withdrew consent and two missed follow-up appointments, resulting in 141 patients in the primary analysis. Of these, 41 received intensive medical therapy alone, 50 underwent gastric bypass, and 50 underwent sleeve gastrectomy. Baseline characteristics were fairly similar between the three arms. The baseline mean HbA1c was 9%, the mean duration of DM was about 8.3 years, and 53% were on ≥3 diabetes medications (insulin use in about 47% of total). The mean body mass index (BMI) was 36 kg/m2, with 34% having a BMI <35 kg/m2. About 92% had metabolic syndrome.

The primary endpoint of achieving HbA1c ≤6% at 12 months was significantly higher in the gastric bypass and sleeve gastrectomy arms, as compared with the medical therapy arm (42% vs. 37% vs. 12%, p = 0.002 and p = 0.008, respectively). No difference was noted between the surgical arms (p = 0.59). Interestingly, all successfully treated patients in the gastric bypass arm did so without the use of any medications, whereas 28% in the sleeve gastrectomy arm required concomitant medications.

Mean change in HbA1c at 12 months from baseline for intensive medical therapy, gastric bypass, and sleeve gastrectomy was -1.4% vs. -2.9% vs. -2.9%, p < 0.001 for both; mean change in body weight from baseline was -5.4 kg vs. -29.4 kg vs. -25.1 kg, p < 0.001 for both. There was a salutary effect on high-density lipoprotein cholesterol (HDL-C) (% change from baseline: 11.3% vs. 28.5% vs. 28.4%, p < 0.001 for both), triglycerides (% change from baseline: -14% vs. -44% vs. -42%, p = 0.002, p = 0.08, respectively), high-sensitivity C-reactive protein (hs-CRP) (% change from baseline: -33.2% vs. -84% vs. -80%, p < 0.001 for both), and number of antihypertensive and lipid-lowering medications required at 12 months as well.

Hypoglycemic episodes were similar between the three arms (81% vs. 56% vs. 80%). Reoperations were necessary in 6% of gastric bypass and 2% of gastrectomy patients. Anastomotic ulcers developed in 8% of gastric bypass patients. Other surgery-related complications were minor.

Three-year follow-up: HbA1c ≤6% was still higher in the gastric bypass and sleeve gastrectomy arms, as compared with the medical therapy arm (38% vs. 24% vs. 5%, p < 0.001 and p = 0.01, respectively). Glycemic relapse (HbA1c controlled ≤6% at 1 year, but not at 3 years) was lowest in the gastric bypass arm (24% vs. 50% vs. 80%, p = 0.03 and p = 0.34, respectively). There was a linear association between achieving the primary endpoint and BMI (1.41, 95% confidence interval 1.22-1.64, p < 0.001). Mean change in body weight from baseline was highest in the gastric bypass arm (-26.2% vs. -21.3% vs. -4.3%, p < 0.001 for both).

There were significant improvements in five of eight mental and physical domains among patients in the gastric bypass group and in two of eight domains among patients in the sleeve gastrectomy group, as compared with the medical therapy group. These included improved overall general health and increased energy. The beneficial effect on HDL levels with gastric bypass was maintained (34.7% vs. 35.0% vs. 4.6%, p < 0.001). Urinary albumin-to-creatinine ratio showed a higher decline in the gastric bypass arm. No additional surgical procedures were necessary in the two surgical arms.

Interpretation:

The results of this trial indicate that intensive medical therapy + bariatric surgery is superior to intensive medical therapy alone in achieving adequate glycemic control of type 2 DM in obese or overweight patients. Both gastric bypass and sleeve gastrectomy seem to achieve similar results. Complications were slightly higher with gastric bypass, but overall success seemed to be numerically higher than sleeve gastrectomy (including the finding that all patients who achieved an HbA1c ≤6% in the gastric bypass arm did so without the use of concomitant diabetes medications).

Long-term follow-up results indicate sustained beneficial effects at 3 years, with somewhat better results with gastric bypass over sleeve gastrectomy. These findings have large public health ramifications, and if confirmed by multicenter trials (the current trial was conducted at one quaternary medical center with one surgeon performing all bariatric procedures), could prove to be a very viable option in obese or overweight patients with poorly controlled type 2 DM.

Study Design:

Randomized. Blinded. Parallel.

Primary Endpoints:

  • HbA1c ≤6% at 12 months

Secondary Endpoints:

  • HbA1c ≤6% without the use of DM medications
  • Changes in fingerstick blood glucose at 12 months
  • Change in BMI at 12 months
  • % change in HDL-C from baseline
  • % change in triglycerides from baseline
  • % change in hs-CRP from baseline
  • Change in medications from baseline
  • Safety and adverse events

 

Patient Population:

  • Age 20-60 years
  • Diagnosed DM with HbA1c >7%
  • BMI 27-43 kg/m2 

    Number of screened applicants: 218
    Number of enrollees: 150
    Duration of follow-up: 12 months and 3 years 
    Mean patient age: 49 years
    Percentage female: 66%

Exclusions:

  • Prior bariatric surgery or other complex abdominal surgery
  • Poorly controlled medical or psychiatric disorders

References:

Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012;366:1567-76.

Presented by Dr. Philip Schauer at ACC.12 & ACC-i2 with TCT, Chicago, IL, March 26, 2012.

Schauer PR, Bhatt DL, Kirwan JP, et al., on behalf of the STAMPEDE Investigators. Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 3-Year Outcomes. N Engl J Med 2014;370:2002-12.

Presented by Dr. Philip R. Schauer at the American College of Cardiology Scientific Session, Washington, DC, March 30, 2014.

Advertisement
Advertisement