Efficacy of omarigliptin,once-weekly dipeptidyl peptidase-4 inhibitor,in patients with type 2 diabetes

BACKGROUND Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors(DPP-4is).Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice,data regarding its efficacy in patients with type 2 diabetes(T2D)after switching are limited.AIM To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents.METHODS Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is:switched from linagliptin,switched from sitagliptin,and switched from vildagliptin.During a 3-mo follow-up,the clinical parameters among these groups were assessed and compared,with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups.RESULTS Hemoglobin A1c levels saw a significant decrease of-0.32%±0.41%in the add-on group(P=0.002).However,the other groups’variables depended on the preswitch daily DPP-4i:switched from linagliptin,-0.05%±0.22%;switched from sitagliptin,-0.17%±0.33%;and switched from vildagliptin,0.45%±0.42%,which saw significant worsening(P=0.0007).Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control(P=0.0013).The mean and standard deviation of sensor glucose value,the mean amplitude of glycemic excursions,and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin.However,in patients switched from vildagliptin,not only did the glucose variability indices see no improvements,the mean of daily difference even underwent significant worsening.CONCLUSION Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin,but not vildagliptin,improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients.

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome

Background:Obesity and insulin resistance(IR)are common features of polycystic ovary syndrome(PCOS).Metformin(MET)increases insulin sensitivity,but it is associated with unsatisfactory weight loss.The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes.This study aimed to explore the therapeutic effects of exenatide once-weekly(QW)combined with MET on body weight,as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups:MET(500 mg three times a day[TID])or combination treatment(COM)(MET 500 mg TID,exenatide 2 mg QW)for 12 weeks.The primary outcomes were anthropometric changes associated with obesity,and the secondary outcomes included changes in reproductive hormone levels,glucose and lipid metabolism,and C-reactive protein.Results:Forty(80%)patients completed the study.COM therapy was superior to MET monotherapy in reducing weight(P=0.045),body mass index(BMI)(P=0.041),and waist circumference(P=0.023).Patients in the COM group on an average lost 3.8±2.4 kg compared with 2.1±3.0 kg in the MET group.In the COM group,BMI and waist circumference decreased by 1.4±0.87 kg/m2 and 4.63±4.42 cm compared with 0.77±1.17 kg/m2 and 1.72±3.07 cm in the MET group,respectively.Moreover,levels of fasting glucose,oral glucose tolerance test(OGTT)2-h glucose,and OGTT 2-h insulin were significantly lower with COM therapy than with MET(P<0.050).Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusions:COM therapy was more effective than MET alone in reducing body weight,BMI,and waist circumference,and improving insulin sensitivity in overweight/obese women with PCOS,with acceptable short-term side effects.