Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Once Daily Empagliflozin 25 mg for the Treatment of Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass.

Aims: To investigate the effect of empagliflozin on glucose dynamics in individuals suffering from postbariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). Methods: Twenty-two adults with PBH after RYGB were randomized to empagliflozin 25 mg or placebo once daily over 20 days in a randomized, double-blind, placebo-controlled, crossover trial. The primary efficacy outcome was the amplitude of plasma glucose excursion (peak to nadir) during a mixed-meal tolerance test (MMTT). Outcomes of the outpatient period were assessed using continuous glucose monitoring (CGM) and an event-tracking app. Results: The amplitude of glucose excursion during the MMTT was 8.1 ± 2.4 mmol/L with empagliflozin versus 8.1 ± 2.6 mmol/L with placebo (mean ± standard deviation, P = 0.807). CGM-based mean amplitude of glucose excursion during the 20-day period was lower with empagliflozin than placebo (4.8 ± 1.3 vs. 5.2 ± 1.6. P = 0.028). Empagliflozin reduced the time spent with CGM values >10.0 mmol/L (3.8 ± 3.5% vs. 4.7 ± 3.8%, P = 0.009), but not the time spent with CGM values <3.0 mmol/L (1.7 ± 1.6% vs. 1.5 ± 1.5%, P = 0.457). No significant difference was observed in the quantity and quality of recorded symptoms. Eleven adverse events occurred with empagliflozin (three drug-related) and six with placebo. Conclusions: Empagliflozin 25 mg reduces glucose excursions but not hypoglycemia in individuals with PBH. Clinical Trial Registration: Clinicaltrials.gov: NCT05057819.

Fostering physical activity-related health competence after bariatric surgery with a multimodal exercise programme: A randomised controlled trial.

Regular physical activity (PA) supports the long-term success of bariatric surgery. However, integrating health-enhancing physical activity in daily life requires specific competences. In this study, we evaluated a multimodal exercise programme to build these competences.Forty adults who underwent bariatric surgery were randomised to a multimodal exercise programme or control group. Primary outcomes were the facets of PA-related health competences, namely the control competence for physical training, PA-specific affect regulation, motivational competence and PA-specific self-control. Secondary outcomes were PA behaviour and subjective vitality. Outcomes were assessed before, directly after the intervention and at 3 months follow-up.Significant treatment effects were found for control competence for physical training and PA-specific self-control but not for PA-specific affect regulation and motivational competence. Significant treatment effects were further observed for self-reported exercise and subjective vitality, all in favour of the intervention group. In contrast, no treatment effect was found for device-based PA. Overall, this study provides a foundation for future research to optimise long-term post bariatric surgery outcomes.

Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals.

AIMS/HYPOTHESIS: Post-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes during insulin-induced postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia after Roux-en-Y gastric bypass vs surgical and non-surgical control individuals. METHODS: In this case-control study, 32 adults belonging to four groups with comparable age, sex and BMI (patients with post-bariatric hypoglycaemia, Roux-en-Y gastric bypass, sleeve gastrectomy and non-surgical control individuals) underwent a postprandial hypoglycaemic clamp in our clinical research unit to reach the glycaemic target of 2.5 mmol/l 150-170 min after ingesting 15 g of glucose. Glucose fluxes were assessed during the postprandial and hypoglycaemic period using a dual-tracer approach. The primary outcome was the incremental AUC of glucagon during hypoglycaemia. Catecholamines, cortisol, growth hormone, pancreatic polypeptide and endogenous glucose production were also analysed during hypoglycaemia. RESULTS: The rate of glucose appearance after oral administration, as well as the rates of total glucose appearance and glucose disappearance, were higher in both Roux-en-Y gastric bypass groups vs the non-surgical control group in the early postprandial period (all p<0.05). During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups vs the non-surgical control group (all p<0.01). Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia vs the non-surgical control group (median [IQR]: 24.7 [10.9, 38.7] pmol/l vs 238.7 [186.3, 288.9] pmol/l) (p=0.005). Other hormonal responses to hypoglycaemia and endogenous glucose production did not significantly differ between the groups. CONCLUSIONS/INTERPRETATION: The glucagon response to insulin-induced postprandial hypoglycaemia is lower in post-bariatric surgery individuals compared with non-surgical control individuals, irrespective of the surgical modality. No significant differences were found between patients with post-bariatric hypoglycaemia and surgical control individuals, suggesting that impaired counter-regulation is not a root cause of post-bariatric hypoglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04334161.

The impact of postbariatric hypoglycaemia on driving performance: A randomized, single-blind, two-period, crossover study in a driving simulator.

Postbariatric hypoglycaemia (PBH) is an increasingly recognized complication of bariatric surgery, but its effect on daily functioning remains unclear. In this randomized, single-blind, crossover trial we assessed driving performance in patients with PBH. Ten active drivers with PBH (eight females, age 38.2 ± 14.7 years, body mass index 27.2 ± 4.6 kg/m2 ) received 75 g glucose to induce PBH in the late postprandial period and aspartame to leave glycaemia unchanged, on two different occasions. A simulator was driven during 10 minutes before (D0) and 20 (D1), 80 (D2), 125 (D3) and 140 minutes (D4) after the glucose/aspartame ingestion, reflecting the expected blood glucose (BG) increase (D1), decrease (D2) and hypoglycaemia (D3, D4). Seven driving features indicating impaired driving were integrated in a Bayesian hierarchical regression model to assess the difference in driving performance after glucose/aspartame ingestion. Mean ± standard deviation peak and nadir BG after glucose were 182 ± 24 and 47 ± 14 mg/dL, while BG was stable after aspartame (85 ± 4 mg/dL). Despite the lack of a difference in symptom perception, driving performance was significantly impaired after glucose versus aspartame during D4 (posterior probability 98.2%). Our findings suggest that PBH negatively affects driving performance.

Prospective evaluation and 7-year follow-up of Swedish adjustable gastric banding in adults with extreme obesity.

BACKGROUND: Swedish adjustable gastric banding (SAGB) is a widespread laparoscopic procedure in bariatric surgery. Few long-term data is available. AIM: To determine long-term outcome after SAGB in 196 patients studied prospectively. PATIENTS AND METHODS: 196 patients, 40 men, and 156 women have been operated from 1996 to 2005. Age was 38 +/- 1 (mean +/- sem) years. Mean follow-up was 63 +/- 2 months. RESULTS: Hospital morbidity was 3% (0.5% early reoperation); mortality was 0. Late complications were band migration (1%), leakage (5%), slipping (4%), or pouch dilatation (8%). Minor reoperations (tube replacement, port-related, and hernias) were needed in 7.5%. Cumulative major reoperation rate reached 32%. Eighteen percent had a band replacement; 14% had removal of band anatomy. Late mortality was 0.5%. Exactly 7 years after SAGB, BMI decreased from 45 +/- 1 kg/m2 to 33 +/- 1 kg/m2, and excess weight loss (EWL) was 61 +/- 4%. Sixty-eight percent of the patients reached > or = 50% EWL. CONCLUSION: In 14% of the patients, the band anatomy had to be removed. Seven years of intact band anatomy leads to a successful EWL of 61 +/- 4% and to EWL of > or = 50% in 68%. However, cumulative major reoperation rate of 32% in 7 years makes it mandatory to offer and discuss other bariatric procedures to the respective patients.