Background/Objectives: Hypoglycemic effect of camel milk supplementation in experimental rat model and significant reduction in doses of insulin in type 1 diabetic patients have been observed in our previous studies. This long-term study was undertaken to assess the efficacy, safety and acceptability of camel milk as an adjunct to insulin therapy in type 1 diabetics. Subjects/Methods: In this 2-year randomized clinical, parallel design study, 24 type 1 diabetics were enrolled and divided into two groups. Group I (n ¼ 12) received usual care, that is, diet, exercise and insulin and Group II (n ¼ 12) received 500 ml camel milk in addition to the usual care. Insulin requirement was titrated weekly by blood glucose estimation. Results were analyzed by using the regression technique. Results: In camel milk group, there was decrease in mean blood glucose (118.58 ± 19-93.16 ± 17.06 mg/dl), hemoglobin A1c levels (7.81 ± 1.39-5.44 ± 0.81%) and insulin doses (32.50 ± 9.99-17.50 ± 12.09 U/day, Po0.05). Out of 12 subjects receiving camel milk, insulin requirement in 3 subjects reduced to zero. There was nonsignificant change in plasma insulin and anti-insulin antibodies in both the groups. Conclusion: It may be stated that camel milk is safe and efficacious in improving long-term glycemic control, with a significant reduction in the doses of insulin in type 1 diabetic patients.

Aims To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine. Materials and methods Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase‐4 (DPP‐4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP‐4 inhibitors and sulphonylureas) and stabilized during a run‐in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L. Results A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and −20.5 mmol/mol (−1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and −15.5 mmol/mol (−1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was −5.0 mmol/mol (−0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups. Conclusion When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. http://ClinicalTrials.gov Identifier: NCT02738879.

DPP-4 inhibitors (DPP-4is) are often discontinued with initiation of insulin therapy but the impact of this discontinuation on efficacy and hypoglycemia has not been studied. In this double-blind trial the safety and efficacy of initiating insulin while continuing sitagliptin (SITA) was evaluated. Eligible patients had inadequately controlled T2DM on metformin (MET, ≥ 1500 mg/day) in dual or triple combination therapy with a DPP-4i and/or sulfonylurea. Those on MET + SITA (100 mg/day) directly entered the trial; all others were switched to MET + SITA and stabilized during a run-in period. Subjects were randomized to continuing SITA or discontinuing SITA and switching to matching placebo, with both groups initiating insulin (LANTUS®), which was titrated based on fasting glucose. 746 subjects (mean A1C 8.8%, disease duration 10.6 years) were randomized. After 30 weeks, continuing SITA was superior to discontinuing SITA in reducing A1C (p&lt;0.001). Patients who continued SITA had a lower event rate of documented symptomatic hypoglycemia (blood glucose ≤70 mg/dL) and daily insulin dose compared to patients who discontinued SITA. Summary adverse event measures and change in body weight (week 30) were similar in the 2 treatment groups. In summary, with the initiation of insulin therapy, continuation of SITA resulted in superior glycemic efficacy and less documented symptomatic hypoglycemia.Change from Baseline in A1C (%) aTreatmentLS Mean (95% CI)Difference in LS Means (95% CI)SITA, n= 373-1.88 (-1.98, -1.78)-0.46 (-0.58, -0.34)PBO, n= 370-1.42 (-1.52, -1.32)Event Rate of Documented Symptomatic Hypoglycemia (Blood Glucose ≤70 mg/dL) b, cTreatmentEvent Rate (95% CI)Event Rate Ratio (95% CI)SITA, n= 3711.55 (1.22, 1.96)0.73 (0.54, 0.98)PBO, n= 3702.12 (1.70, 2.66)Total Daily Insulin Dose (Units) a, dTreatmentLS Mean (95% CI)Difference in LS Means (95% CI)SITA, n= 36553.2 (48.5, 58.0)-8.0 (-14.6, -1.5)PBO, n= 36761.3 (56.5, 66.0)a Analyzed using a longitudinal data analysis modelb Analyzed using a negative binominal regression modelc Two subjects (both in the sitagliptin group) were not included in the analysis due to a missing value of a model covariate (race)d 11 subjects did not have post baseline insulin dose data Disclosure R. Roussel: Advisory Panel; Self; AbbVie Inc., Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, AstraZeneca. Speaker's Bureau; Self; Servier. Consultant; Self; Bayer AG. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Amgen Inc., Sanofi, Novo Nordisk A/S, Danone Research. Stock/Shareholder; Self; Iriade. Advisory Panel; Self; Physiogenex S.A.S.. S. Duran-Garcia: None. Y. Zhang: None. S. Shah: Employee; Self; Merck & Co., Inc. C. Darmiento: Employee; Self; Merck & Co., Inc. R. Shankar: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; NGM Biopharmaceuticals. E.A. O'Neill: Employee; Self; Merck & Co., Inc. G.T. Golm: Employee; Self; Merck & Co., Inc. R.L. Lam: Employee; Self; Merck & Co., Inc. I. Gantz: Employee; Self; Merck Sharp & Dohme Corp. K.D. Kaufman: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc..

Background We examined the efficacy and safety of corifollitropin alfa (CFA) combined with human chorionic gonadotropin (hCG) for the induction of testicular growth and pubertal development in adolescent boys with hypogonadotropic hypogonadism (HH). Methods This was a 64-week, multi-center, open-label, single-group study of CFA in adolescent males, 14 to &lt;18 years of age, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 μg if weight ≤60 kg, or 150 μg if weight &gt;60 kg) given subcutaneously (SC) once every two weeks (q2wk), after which they entered a 52-week combined treatment period with CFA, q2wk, and SC hCG, twice-weekly (hCG dose adjusted between 500 IU and 5,000 IU to keep total testosterone and estradiol levels within protocol-specified ranges). The primary efficacy endpoint was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. Results After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 [95% CI: 7.44, 11.97] (arithmetic mean of change from baseline at Week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. Conclusions Treatment of adolescent males with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased testosterone, and a pubertal growth spurt. (EudraCT: 2015-001878-18)