AimsTreatment with liraglutide 3.0 mg has been associated with gallbladder‐related adverse events. To conduct a single‐centre, double‐blind, 12‐week trial comparing the effect of 0.6 mg liraglutide and steady‐state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes.MethodsParticipants were randomized 1:1 to once‐daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6‐mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600‐kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12‐week maximum postprandial gallbladder ejection fraction (GBEFmax), measured over 240 minutes after starting the meal.ResultsBaseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2, 50% women). Mean 12‐week GBEFmax (treatment difference −3.7%, 95% confidence interval [CI] −13.1, 5.7) and area under the GBEF curve in the first 60 minutes (−390% × min, 95% CI −919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11‐240) minutes with liraglutide 3.0 mg and 77 (22‐212) minutes with placebo. Similar findings were noted after the first 0.6‐mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events.ConclusionsTreatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax.

No abstract

A series of 518 patients with hip fractures and a median age of 78 years was followed for 6 months. On admission to hospital the patients were assessed and were found to be evenly distributed among four social function groups according to their level of dependence on the social welfare system. At the 6 months follow-up the mortality rate was about 16 per cent, leaving 437 patients for a reassessment of social function. The average hospitalization time was 23 days; thus 17 per cent of all orthopaedic hospital beds in the area were occupied by patients with hip fractures. Patients staying the longest time in hospital were those waiting for discharge to a nursing home. The average stay in rehabilitation institutions was 71 days. The total rehabilitation course was longest for the most dependent patients. The risk of death or deterioration of social function among patients admitted from home was 48 per cent. In the case of social deterioration or technical failure following the fracture treatment the total rehabilitation course was considerably prolonged. The resources required for the treatment of hip fractures in a suburban area of 500,000 inhabitants were calculated to be 32 hospital beds, 43 rehabilitation beds and at least 21 nursing home beds.

Metformin is the most widely used plasma glucose-lowering drug for the treatment of type 2 diabetes. It has been shown that metformin increases plasma concentrations of glucagon-like peptide-1 (GLP-1), but it remains unknown whether metformin-induced GLP-1 secretion plays any role for the beneficial effects of metformin on postprandial glucose metabolism. We investigated the effect of metformin-induced GLP-1 secretion during meal ingestion in patients with type 2 diabetes using the GLP-1 receptor antagonist exendin[9-39]. In a double-blinded, double dummy, placebo-controlled, randomized, cross-over study, 15 participants with type 2 diabetes (medians: age 71 years, BMI 30.07 kg/m2, HbA1c 50 mmol/mol) were subjected to 14 days’ metformin and placebo treatment, respectively, in randomized order with at least a 2-week washout period between treatments. At the end of each treatment period, two randomized 4-hour mixed meal tests with either concomitant exendin[9-39] (450 pmol/kg/min) or saline infusion, were carried out. Metformin treatment significantly lowered fasting plasma glucose and postprandial plasma glucose excursions compared to placebo. We observed equal metformin-induced reductions in postprandial plasma glucose excursions during saline and exendin[9-39] infusions. Based on postprandial plasma glucose excursions, using the GLP-1 receptor antagonist exendin[9-39], we cannot confirm that GLP-1 secretion is involved in the beneficial postprandial glucose-lowering effects of metformin in patients with type 2 diabetes. Disclosure L.S. Hansen: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. A. Brønden: None. N.B. Dalsgaard: None. E. Bahne: None. P.H. Sørensen: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics. T. Vilsbøll: Advisory Panel; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Consultant; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Research Support; Self; Eli Lilly and Company, Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Amgen Inc.. Advisory Panel; Self; MedImmune, Sanofi. Consultant; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi.