Background: Obesity surgery is effective for obesity and type 2 diabetes (T2DM). However, many patients do not achieve sustained diabetes remission following surgery. Liraglutide, a GLP-1 analogue, improves glycaemia and reduces body weight. Our aim was to evaluate the safety and effectiveness of Liraglutide 1•8 mg in patients with persistent or recurrent T2DM after surgery. Methods: In this double-blind, placebo-controlled trial, adults with HbA1c >48 mmol/mol (>6•5%) at least one year after surgery were randomised 2:1 to once-daily subcutaneous Liraglutide 1•8 mg or Placebo, together with a reduced-calorie diet and increased physical activity. The primary outcome was the change in HbA1c from baseline to 26 weeks. EudraCT 2014-003923-23 and ISRCTN 13643081. Findings: Between February 2016 and November 2018, we assigned 80 patients to receive Liraglutide (n=53) or Placebo (n=27). Seventy-one (89%) participants completed the study up to week 26 (complete-cases population). A multivariable linear regression analysis taking baseline HbA1c and type of surgery into account as covariates showed that Liraglutide was associated with a difference in HbA1c change of-13•3 mmol/mol or-1•22%, 95% CI-19•7 to-7•0, p<0•001) vs Placebo at 26 weeks. Liraglutide was associated with a difference in the change of weight of-4•23 kg [95% CI-6•81 to-1•64, p<0•001) vs Placebo. No significant influence of type of surgery was noted. Interpretation: This is the first randomised controlled trial of adjunctive Liraglutide treatment in patients with diabetes mellitus after metabolic surgery. The results support the use of Liraglutide therapy in this clinical context. Funding: JP Moulton Charitable Foundation 3 surgery. We have previously shown that the acute peripheral administration of the GLP-1 RA Exendin-4 in rodent models of RYGB has additive effects to the already enhanced endogenous GLP-1 secretion as demonstrated by an additional reduction in food intake 11. Indeed, data from retrospective non-randomised studies in humans support this hypothesis: the administration of GLP-1 RAs in patients with and without T2DM and a suboptimal response to metabolic surgery was associated with weight loss and glycaemic improvements 12-15. This RCT was therefore designed to investigate the safety and efficacy of pharmacological administration of the GLP-1 RA Liraglutide on glycaemic control in patients with persistent or recurrent T2DM after RYGB or VSG surgery. Methods Study population This was a prospective randomised double-blinded placebo-controlled clinical trial. Eighty patients with obesity and persistent or recurrent T2DM that had undergone RYGB or VSG surgery at least 12 months before randomisation were recruited from the

Purpose Ipilimumab, a monoclonal antibody inhibiting CLTA-4, is an established treatment in metastatic melanoma, either alone or in combination with nivolumab, and results in immune mediated adverse events, including endocrinopathy. Hypophysitis is one of the most common endocrine abnormalities. An early recognition of hypophysitis may prevent life threatening consequences of hypopituitarism; therefore, biomarkers to predict which patients will develop hypophysitis would have clinical utility. Recent studies suggested that a decline in TSH may serve as an early marker of IH. This study was aimed at assessing the utility of thyroid function tests in predicting development of hypophysitis. Methods A retrospective cohort study was performed for all patients ( n = 308) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. Thyroid function tests, other pituitary function tests and Pituitary MRIs were used to identify those with hypophysitis. Results and conclusions Ipilimumab-induced hypophysitis (IH) was diagnosed in 25 patients (8.15%). A decline in TSH was observed in hypophysitis cohort during the first three cycles but it did not reach statistical significance ( P = 0.053). A significant fall in FT4 ( P < 0.001), TSH index ( P < 0.001) and standardised TSH index ( P < 0.001) prior to cycles 3 and 4 in hypophysitis cohort was observed. TSH is not useful in predicting development of IH. FT4, TSH index and standardised TSH index may be valuable but a high index of clinical suspicion remains paramount in early detection of hypophysitis. Electronic supplementary material The online version of this article (10.1007/s40618-020-01297-3) contains supplementary material, which is available to authorized users.

IntroductionObesity and type 2 diabetes are commonly seen together in current clinical practice. Morbid obesity and poorly controlled diabetes is often a therapeutic challenge. Management ideally needs to target insulin resistance and hormonal control mechanisms. When subcutaneous insulin is used in patients with obesity and type 2 diabetes, it exacerbates weight gain and thus a vicious cycle of worsening insulin resistance requires additional management strategies.We report a case of exaggerated weight reduction with combination therapy of liraglutide and dapagliflozin. The patient achieved a loss in excess body weight (EBW) of 73.5 kg or 40.3% and a reduction in HbA1c from 83 mmol/mol (9.7%) to 36 mmol/mol (5.4%) in response to the combination therapy of oral dapagliflozin with subcutaneous liraglutide and concurrent discontinuation of subcutaneous insulin.

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