Metabolic surgery trumps medication, lifestyle intervention in T2D control

Metabolic surgery may be a suitable treatment option for type 2 diabetes (T2D), with a greater likelihood of remission, lower requirement for glucose-control medications, and fewer diabetes-related complications compared with medical therapy, according to long-term follow-up of a small Italian trial.

“The results of our study showed that metabolic surgery is more effective than medical and lifestyle interventions in the long-term control of T2D, [resulting] in durable remission of T2D, … a significantly greater reduction in HbA_1c concentrations from baseline, … lower coronary heart disease risk, better kidney function, better quality of life, reduced medication use, and lower incidence of diabetes-related complications,” the authors noted.

Participants in this open-label, single-centre study were 60 patients aged 30–60 years who had T2D for >5 years (HbA_1c ≥7.0 percent) and BMI ≥35 kg/m². They were randomized 1:1:1 to undergo Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion (BPD), or receive medical therapy, in addition to individualized lifestyle interventions.

At baseline, age, sex, glycaemic control, diabetes duration, BMI, bodyweight, or use of insulin or glucose-lowering medications did not differ between groups.

 

Multiple outcome improvement

None of the patients who received medical therapy experienced remission (HbA_1c <6.5 percent and fasting plasma glucose <100 mg/dL without medication for ≥1 year). [Lancet 2021;397:293-304]

Of the 57 patients who completed 10-year follow-up, 15 (37.5 percent) who underwent surgical therapy maintained their T2D remission, specifically 10 and five patients who underwent BPD and RYGB, respectively (per-protocol analysis; 50.0 and 25.0 percent, respectively; p=0.19 between surgical procedures).

Patients who did not experience remission in the first 2 years post-surgery did not proceed to remission in the longer term. Of the 34 patients who experienced diabetes remission at 2 years, 20 (58.8 percent) experienced a relapse of hyperglycaemia over the 10-year follow-up, including 52.6 and 66.7 percent of patients who underwent BPD and RYGB, respectively (10 in each group). The risk of relapse was greatest within 5 years post-surgery.

Nonetheless, despite a reduction in the use of glucose-control medications, adequate glycaemic control at 10 years was maintained by all patients who experienced relapse (mean HbA_1c 6.7 percent).

Surgically-treated patients required fewer glucose-control medications at 10 years than medically-treated ones (mean 0.7 [BPD] and 1.4 [RYGB] vs 2.9; p<0.0010). Insulin requirement was also reduced 10 years post-surgery, with 2.5 percent of surgery recipients requiring insulin vs 53.3 percent of medical therapy recipients.

Diabetes-free survival was a median 9 and 5 years among patients who underwent BPD and RYGB, respectively, with no significant difference between groups (p=0.25).

Mean HbA_1c at 10 years was lower among BPD and RYGB compared with medical therapy recipients (6.4 and 6.7 percent vs 7.6 percent; p<0.0001).

Glycaemic control among medical therapy recipients was greater at 10 years compared with baseline, though HbA_1c improvement from baseline was greater post-surgery than with medical therapy (-2.4 percent [BPD] and -1.9 percent [RYGB] vs -0.8 percent; p<0.0097). In addition, 87.5 percent of patients who underwent surgery met the target HbA_1c of <7.0 percent compared with none of the medical therapy recipients.

At 10 years, body weight was significantly reduced following surgery vs medical therapy (-29.2 percent [BPD] and -28.0 percent [RYGB] vs -4.2 percent), though there was minor weight regain after year 2 in those who underwent surgery (6.6 and 5.4 kg in the RYGB and BPD groups, respectively).

Insulin sensitivity, as per HOMA-IR* scores, was greater among surgery than medical therapy recipients, with lower scores among those who maintained remission vs relapsed (mean 1.3 vs 1.8; p=0.034).

Estimated glomerular filtration rate (eGFR) at 10 years was better in the surgical (mean difference 1.6 [BPD] and 15.5 [RYGB] mL/min/1.73 m²; p=0.0004) vs medical therapy group.

Plasma triglyceride levels were lower among surgery vs medical therapy recipients, and total and LDL-cholesterol levels lower among BPD vs RYGB or medical therapy recipients. The greatest increase in HDL-cholesterol occurred among RYGB recipients.

The risk of diabetes-related complications was lower among surgery vs medical therapy recipients (5.0 percent vs 72.2 percent; relative risk, 0.07, 95 percent confidence interval [CI], 0.01–0.48 for both BPD and RYGB vs medical therapy).

Patients who underwent BPD more frequently experienced serious adverse events compared with medical therapy recipients (odds ratio [OR], 2.7, 95 percent CI, 1.3–5.6), though the risk was lower among those who underwent RYGB vs medical therapy (OR, 0.7, 95 percent CI, 0.3–1.9). Iron deficiency and mild osteopenia occurred post-surgery and were more frequent in BPD recipients.

 

Findings establish long-term benefit of surgery

“The availability of all patients who underwent surgery for the 10-year analysis … provides robust information about the durability of surgically-induced diabetes remission in patients with advanced T2D,” said the authors. “[The results also suggest] that T2D is a potentially curable disease.”

“Our study confirms, in the context of a randomized controlled trial, that metabolic surgery is more effective than alternative treatment strategies at delaying disease progression and preventing macrovascular and microvascular complications of T2D, as previously suggested in other non-randomized studies,” they said.

“Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and T2D,” they concluded.