Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial.

AIM: The aim of this trial was to evaluate the efficacy and safety of the combination of once-daily insulin detemir (IDet) and sitagliptin (SITA) versus SITA ± sulphonylurea (SU), both in combination with metformin (MET) in insulin-naive subjects. METHODS: In a 26-week, open-label, randomized, parallel-group study in type 2 diabetes, insulin-naive subjects concomitantly treated with MET ± second oral antidiabetic drug (OAD) were randomized 1 : 1 to IDet + SITA + MET or SITA + MET ± SU. All continued with MET treatment, and those treated with SU continued if randomized to SITA + MET ± SU. Efficacy endpoints included glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), 9-point self-measured plasma glucose (SMPG), weight, body mass index (BMI). Safety endpoints included adverse events (AEs) and hypoglycaemia. RESULTS: Significantly higher reductions in HbA1c, FPG and SMPG were achieved with IDet + SITA + MET compared with SITA + MET ± SU. Estimated HbA1c decreased by 1.44% in the IDet + SITA + MET group versus 0.89% in SITA + MET ± SU, p < 0.001. FPG decreased by 3.7 mmol/l (66.3 mg/dl) versus 1.2 mmol/l (22.2 mg/dl), p < 0.001, respectively. Small decreases in weight and BMI were observed in both arms, with no significant differences. AEs were mild or moderate and were more common in the SITA + MET ± SU arm than in the IDet + SITA + MET arm. There was no major hypoglycaemia. Observed rates of hypoglycaemia were very low (1.3/1.7 episodes/patient year) in both arms. The subgroup treated with MET and SUs prior to the trial achieved similar results. CONCLUSIONS: The combination of once-daily IDet with SITA showed a clinically and significantly better improvement in glycaemic control than SITA in combination with or without SUs. Both regimens were associated with a low rate of hypoglycaemia and slight weight reduction.

A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin.

AIM: To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo. METHODS: A 26-week, multi-country (Canada, Mexico, Romania, South Africa and the USA), randomized, double-blind, placebo-controlled study compared exenatide twice-daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA(1c) 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2-week, single-blind, lead-in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA(1c) change at endpoint (Week 26 or last-observation-carried-forward). RESULTS: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA(1c) significantly more than placebo [-0.84% (s.e. 0.20) vs. -0.10% (0.23), treatment difference -0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, -1.4 (s.e. 0.6) kg vs. placebo, -0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA(1c) and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups. CONCLUSIONS: Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA(1c) without associated hypoglycaemia.

Residents' experiences of abuse, discrimination and sexual harassment during residency training. McMaster University Residency Training Programs.

OBJECTIVE: To assess the prevalence of psychological abuse, physical assault, and discrimination on the basis of gender and sexual orientation, and to examine the prevalence and impact of sexual harassment in residency training programs. DESIGN: Self-administered questionnaire. SETTING: McMaster University, Hamilton, Ont. PARTICIPANTS: Residents in seven residency training programs during the academic year from July 1993 to June 1994. Of 225 residents 186 (82.7%) returned a completed questionnaire, and 50% of the respondents were women. OUTCOME MEASURES: Prevalence of psychological abuse, physical assault and discrimination on the basis of gender and sexual orientation experienced by residents during medical training, prevalence and residents' perceived frequency of sexual harassment. RESULTS: Psychological abuse was reported by 50% of the residents. Some of the respondents reported physical assault, mostly by patients and their family members (14.7% reported assaults by male patients and family members, 9.8% reported assaults by female patients and family members), 5.4% of the female respondents reported assault by male supervising physicians. Discrimination on the basis of gender was reported to be common and was experienced significantly more often by female residents than by male residents (p < 0.01). Ten respondents, all female, reported having experienced discrimination on the basis of their sexual orientation. Most of the respondents experienced sexual harassment, especially in the form of sexist jokes, flirtation and unwanted compliments on their dress or figure. On average, 40% of the respondents, especially women (p < 0.01), reported experiencing offensive body language and receiving sexist teaching material and unwanted compliments on their dress. Significantly more female respondents than male respondents stated that they had reported events of sexual harassment to someone (p < 0.001). The most frequent emotional reactions to sexual harassment were embarassment (reported by 24.0%), anger (by 23.4%) and frustration (20.8%). CONCLUSION: Psychological abuse, discrimination on the basis of gender and sexual harassment are commonly experienced by residents in training programs. A direct, progressive, multidisciplinary approach is needed to label and address these problems.

Attitudes toward the use of gender-inclusive language among residency trainees. The McMaster Residency Training Program Directors.

OBJECTIVE: To explore postgraduate medical trainees' attitudes toward the use of gender-inclusive language. DESIGN: Self-administered questionnaire. SETTING: Seven residency training programs at McMaster University, Hamilton, Ont., from July 1993 to June 1994. PARTICIPANTS: Of 225 residents in the programs, 186 responded to the survey, for a response rate of 82.7%. Men and women were equally represented among the respondents. OUTCOME MEASURES: Categorization of attitudes about the use of language as gender-inclusive or gender-exclusive; characteristics predicting a gender-inclusive attitude. RESULTS: Factor analysis and Cronbach's alpha (0.90) supported the existence of a construct related to attitudes about language use, the poles of which were categorized as gender-inclusive and gender-exclusive. The authors classified residents with respect to their attitudes to language use from their responses to the questionnaire. In univariate analyses, sex, residency program and country of graduation significantly predicted a gender-inclusive attitude (p < 0.01). Only the first 2 variables were significant in a multivariate model; residency program explained 18% of the variance and sex 3%. Residents in obstetrics and gynecology and psychiatry had the most gender-inclusive attitudes, whereas residents in surgery and anesthesia had the most gender-exclusive attitudes. CONCLUSIONS: Residents' values are reflected in the language they choose to use. Language use may provide an index of underlying attitudes that may create hostile environments for female trainees.