Objective To assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW). Research design and methods Post hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O ( NCT02058147 ; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L ( NCT02058160 ; inadequately controlled patients on basal insulin; NA, n=196; RoW, n=535). Efficacy outcomes were: change from baseline to Week 30 in glycated hemoglobin (HbA1c), postprandial glucose (PPG), PPG excursions, fasting plasma glucose (FPG) and body weight; proportion of patients achieving HbA1c <42 mmol/mol (<7.0%); proportion of patients achieving composite endpoint: HbA1c <42 mmol/mol (<7.0%), no weight gain or symptomatic hypoglycemia (blood glucose ≤3.9 mmol/L (≤70 mg/dL)). Safety endpoints included incidence of documented symptomatic hypoglycemia and gastrointestinal (GI) adverse events. Results Significantly larger reductions (p≤0.003) in HbA1c from baseline to Week 30 were achieved with iGlarLixi, compared with iGlar or lixisenatide, in NA and RoW patients in LixiLan-O (iGlarLixi vs iGlar: −0.31 and −0.29, respectively; iGlarLixi vs lixisenatide: −0.84 and −0.69, respectively) and in LixiLan-L (iGlarLixi vs iGlar: −0.5 and −0.51, respectively). Documented symptomatic hypoglycemia was similar between NA and RoW patients. iGlarLixi resulted in significant weight benefits versus iGlar (change from baseline –1.58 and –1.29 kg for NA and RoW patients, respectively; p < 0.001). GI adverse events were similar for iGlarLixi and iGlar, but significantly higher for lixisenatide. Conclusions iGlarLixi improved glycemic parameters versus iGlar or lixisenatide alone in both NA and RoW patients, with beneficial weight effects versus iGlar. iGlarLixi treatment responses, hypoglycemia risk and GI adverse events in NA patients were comparable with patients in the RoW. Trial registry Clinicaltrials.gov NCT02058147 and NCT02058160 .-
Objective: To assess efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus (vs) insulin glargine 100 U/mL (Gla-100) in North American and non-North American people with type 2 diabetes mellitus on different background therapies.Methods: A patient-level meta-analysis of three international studies (EDITION 1, 2 and 3) was performed to examine glycemic control and hypoglycemia over 6 months in 2496 participants including 1420 participants in a North American sub-population (Gla-300, N=700; Gla-100, N=720).Endpoints included change in glycated hemoglobin (HbA1c), percentage of patients at target HbA1c at Month 6, incidence and rate of hypoglycemic events, change in body weight and insulin dose, as well as incidence of adverse events.Results: Mean change in HbA1c was comparable for Gla-300 and Gla-100 in both regions (P=0.8347 for treatmentby-subgroup interaction).There were no regional differences in the percentage of participants achieving target HbA1c <7% (53.0 mmol/mol) or <7.5% (58.5 mmol/mol).The cumulative number, the incidence rates, as well as the annualized rates of confirmed (≤3.9 mmol/L and the lower threshold of <3.0 mmol/L) or severe hypoglycemia at any time of the day or during the night were lower with Gla-300 vs Gla-100; this was not affected by the region (all P>0.1).North American participants treated with Gla-300 gained less weight than North American participants treated with Gla-100 (least squares mean change 0.64 kg vs 1.15 kg), whereas in non-North American participants the change in weight tended to be similar in both treatment groups (0.36 kg vs 0.32 kg).Treatment with Gla-300 and Gla-100 was well tolerated in both regions.Conclusion: Gla-300 provided comparable glycemic control to Gla-100 with consistently less hypoglycemia at any time of day and during the night, regardless of the region (North America/outside North America).
There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.
The On Time education program is an innovative, online point-of-care tool designed to uncover and address barriers to insulin initiation, and to facilitate timely insulin initiation, when appropriate, in insulin-naïve individuals with type 2 diabetes (T2D). A total of 195 health care professionals (HCPs) completed online profiles of 1025 insulin-naïve individuals with T2D currently treated with non-insulin antihyperglycemic agents (NIAHAs) and with a glycated hemoglobin (A1C) above the Diabetes Canada target (for most individuals ≤7%). After having completed the discussion tool and questionnaires, participating HCPs were asked to evaluate the program, tool, and questionnaires. Mean age of participants was 61.2 years; 55% were male; mean duration of diabetes was 10.5 years. For the majority of participants (70%) the recommended A1C target was ≤7.0%. On average, participants were prescribed 2.6 NIAHAs, mainly metformin and dipeptidyl peptidase-4 inhibitors. Prior to using the On Time discussion tool, only 23% of individuals with diabetes were judged as likely (16%) or extremely likely (7%) willing to initiate insulin. The leading barriers to initiating insulin were apprehension toward needles/injections (59%), belief that insulin was complicated (56%), and psychological insulin resistance (45%). After using the On Time discussion tool, participants’ perceived willingness to initiate insulin increased (likely: 34%, extremely likely: 28%). Initiation of insulin was planned in 77% of participating individuals. The evaluation questionnaire was completed by 149 HCPs (76.4%), and showed that the discussion tool was perceived to help HCPs address insulin-related barriers (82%), positively impacted their practice (79%), and improved their approach when discussing insulin initiation with individuals with diabetes (76%). Identifying the barriers to initiating insulin and providing educational interventions to address them may help to improve insulin acceptance. Disclosure J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. G. MacNeill: Consultant; Self; Becton, Dickinson and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Sanofi. E.M. Cooke: Other Relationship; Self; Abbott. Speaker's Bureau; Self; Becton, Dickinson and Company, LifeScan Canada. Other Relationship; Self; LifeScan Canada. Speaker's Bureau; Self; Merck & Co., Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi, mdBriefCase Group.P. Filteau: None. M. Vallis: Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; AbbVie Inc.. Advisory Panel; Self; Valeant Pharmaceuticals International, Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. M. Groleau: Employee; Self; Sanofi. P. Javadi: Employee; Self; Sanofi. C. Lebovics: Employee; Self; Sanofi.
