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Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the GLP-1 agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight compared twith placebo, report Jessica Mok, BMBS, MPhil, University College London, UK, and colleagues, does enalapril lower heart rate in their study published online July 26 in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (eg, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.

Extremely Welcome Tools for Severe Obesity

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications…adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku University Hospital, Finland, and Ali Aminian, MD, Cleveland Clinic, Ohio, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Salminen and Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”

Most Patients Had Severe Obesity, Sleeve Gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London, UK, at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index (BMI) of 43 kg/m2 (57% had a BMI ≥ 40 kg/m2). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Salminen has reported receiving personal fees from Novo Nordisk. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

JAMA Surg. Published online July 26, 2023. Article, Editorial

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