Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists.

Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP-1RAs and developing novel GLP-1RA-based co-agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High-dose GLP-1RAs and multi-hormonal strategies including GLP-1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high-dose GLP-1RAs, unimolecular, and multimolecular GLP-1R-based co-agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP-1R-based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide-spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.

Greater Combined Reductions of HbA1c ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators.

INTRODUCTION: A post hoc analysis of the PIONEER 1-5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. METHODS: In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26-78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. RESULTS: Overall, 3506 people in PIONEER 1-5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p < 0.0001), empagliflozin 25 mg (PIONEER 2, p < 0.0001), sitagliptin 100 mg (PIONEER 3, p < 0.0001) and liraglutide 1.8 mg (PIONEER 4, p < 0.0001). Odds of achieving the composite endpoint of HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment were also significantly greater with orally administered semaglutide versus comparators. CONCLUSION: In PIONEER 1-5 and 8, odds of achieving clinically relevant reductions in both HbA1c and body weight were significantly greater with orally administered semaglutide versus comparators.

Cardiovascular Effects of Sodium-Glucose Cotransporter-2 Inhibitors in Adults With Type 2 Diabetes.

Adults with type 2 diabetes mellitus can benefit from pharmacotherapies that lower their risk for cardiovascular disease. This review describes the salient findings from sodium-glucose cotransporter-2 (SGLT2) inhibitor cardiovascular outcome trials that serendipitously revealed the cardiorenal benefits of SGLT2 inhibitors in adults with type 2 diabetes mellitus who either have established cardiovascular disease or multiple cardiovascular risk factors. It also summarizes the findings from other phase 3 clinical studies that measured the cardiovascular effects of SGLT2 inhibitors and real-world evidence reports that compared the cardiovascular impact of SGLT2 inhibitors with other antihyperglycemic agents. The collective data indicate that SGLT2 inhibitors are pleiotropic agents that offer important cardiovascular, metabolic and renal benefits beyond glucose lowering with low incidences of hypoglycemia. Specifically, the placebo-controlled SGLT2 inhibitor cardiovascular outcome trials documented either fewer major adverse cardiac events (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) or a reduction in the composite endpoint of cardiovascular death or hospitalization for heart failure in participants with type 2 diabetes mellitus and established cardiovascular disease. Amongst those with type 2 diabetes mellitus who did not have established cardiovascular disease but did present with multiple risk factors, SGLT2 inhibitors lowered the combined endpoint of cardiovascular death or hospitalization for heart failure but had little impact on the occurrence of major adverse cardiac events. Ongoing clinical trials and subanalyses of the trials that have been reported should shed further light on the clinical benefits and utility of SGLT2 inhibitors.

Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol.

Recent phase 3 clinical trials have evaluated the impact of adding sodium-glucose co-transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non-insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the "STOP DKA Protocol ", an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real-world setting.

In the present multicentre, open-label, prospective, phase III study, we evaluated the real-world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3-mg dose of NG demonstrated real-life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use.

Considerations for Initiating a Sodium-Glucose Co-Transporter 2 Inhibitor in Adults With Type 2 Diabetes Using Insulin.

In order to meet and maintain glycemic control, pharmacological management of individuals with type 2 diabetes typically begins with metformin followed by the introduction of other oral antihyperglycemic agents as needed. In some patients, the aggressive and progressive degeneration of pancreatic ß cell activity means insulin therapy will become a given. The need to routinely monitor blood glucose levels coupled with the undesirable effects associated with insulin-primarily hypoglycemia and weight gain-commonly contribute to physician and patient inertia. The new ß-cell-independent sodium-glucose co-transporter 2 (SGLT2) inhibitors are approved for combination use with all of the currently approved oral and injectable antihyperglycemic classes. The addition of SGLT2 inhibitors to background insulin therapy has the potential to afford many benefits and, in some cases, may reduce the incidence of insulin-associated side effects. This article reviews the available literature on SGLT2 inhibitor-insulin combination therapy and underscores the issues that should be considered prior to introducing SGLT2 inhibitors to individuals with type 2 diabetes who are already on insulin (with or without other antihyperglycemic agents) to ensure individualization of therapy.

Emerging use of combination therapies for the management of type 2 diabetes - focus on saxagliptin and dapagliflozin.

AIMS: The aim of this article is to review the safety and efficacy data of dapagliflozin, saxagliptin, and their combination in the management of patients with type 2 diabetes. Evidence for the use of the single-tablet combination formulation is also presented. METHODS: A nonsystematic literature review was performed using the Ovid, PubMed, and Google Scholar databases. RESULTS: The addition of dapagliflozin/saxagliptin to metformin can lower mean hemoglobin A1c by as much as 1.47% and lead to weight loss of 0.5-2.0 kg. The risk of genital infections with combination therapy is lower than observed with dapagliflozin alone, suggestive of a protective effect. Adverse event risk at 52-week follow-up was not increased beyond that seen with either monotherapy. CONCLUSION: Dapagliflozin/saxagliptin combination is generally well tolerated and is an effective tool in helping patients with diabetes improve glycemic control.

Fast-Acting Insulin Aspart Improves Glycemic Control in Basal-Bolus Treatment for Type 1 Diabetes: Results of a 26-Week Multicenter, Active-Controlled, Treat-to-Target, Randomized, Parallel-Group Trial (onset 1).

OBJECTIVE: This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)-each with insulin detemir. RESULTS: HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart-IAsp, mealtime, -0.15% [95% CI -0.23; -0.07], and postmeal, 0.04% [-0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD -1.18 mmol/L [95% CI -1.65; -0.71], -21.21 mg/dL [-29.65; -12.77]; P < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; P = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose-confirmed (plasma glucose <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes and safety profiles were similar between treatments. CONCLUSIONS: Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.

A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

PURPOSE: The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). METHODS: A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. FINDINGS: The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. IMPLICATIONS: The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile.

SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor-related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor-associated DKA. METHODS: Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel. FINDINGS: DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor-associated DKA may be euglycemic (plasma glucose level <14 mmol/L). DKA is more likely in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. SGLT2 inhibitor-associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended. IMPLICATIONS: Preventive strategies should help avoid SGLT2 inhibitor-associated DKA. All SGLT2 inhibitor-treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol.

Insulin degludec/liraglutide (IDegLira) for the treatment of type 2 diabetes.

The progressive nature of type 2 diabetes necessitates that treatment is intensified as the disease advances. Several studies have shown that basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) can be used in combination to successfully improve glycemic control and this combination is increasingly being considered as an alternative to intensification with prandial insulin. Insulin degludec/liraglutide (IDegLira) is the first fixed-ratio combination of a basal insulin and a GLP-1RA in a single formulation. Here we consider the benefits and potential limitations of such a combination, focusing on the unique modes of action of insulin degludec and the once-daily GLP-1RA liraglutide. IDegLira offers an efficacious combination therapy (mean end-of-trial HbA1c was 6.4-6.9% across the five completed Phase 3 trials), which was well-tolerated in clinical trials. The complementary modes of action resulted in a low rate of hypoglycemia and no weight gain in insulin-treated patients. As a once-daily injection with effects on both fasting and post prandial hyperglycemia, IDegLira has the potential to help many patients reach glycemic target (60-81% of patients achieved HbA1c <7% in clinical trials).

A Study of Diabetes Teaching in Canadian Medical Schools.

PURPOSE: To assess the current status of diabetes teaching in Canadian medical schools. METHODS: Faculty primarily responsible for teaching undergraduate diabetes education were identified at all 17 Canadian medical schools and were asked to provide their undergraduate diabetes curricula. The curricula were analyzed by method of teaching. RESULTS: Reponses were obtained from14 of 17 (82%) medical schools. The average number of teaching hours in the entire undergraduate program was 15.4 and ranged from 7 to 22.5 hours. Formats included lectures, small groups, workshops, assigned readings, problem-based learning and laboratory studies. Lectures made up 48% of the curriculum, followed by small groups at 26%. CONCLUSIONS: There has been an increased use of small group sessions in undergraduate diabetes education, in keeping with generalized changes in medical school curricula. Future study is warranted in assessing the impact of differing undergraduate teaching methods on eventual competency.

Dosing irregularities and self-treated hypoglycemia in type 2 diabetes: results from the Canadian Cohort of an International Survey of Patients and Healthcare Professionals.

OBJECTIVE: Despite their importance in achieving good glycemic control, few real-world data on insulin dosing irregularities and hypoglycemia are available. The multinational, online Global Attitude of Patients and Physicians (GAPP2) survey was conducted to address this situation. METHODS: Insulin-treated patients with type 2 diabetes and healthcare professionals (HCPs) who treat such patients were surveyed in an online cross-sectional study. This article summarizes findings from a sample of the online population in a Canadian cohort of 156 patients and 202 HCPs. RESULTS: A total of 156 patients completed the questionnaires; 26% reported experiencing a dosing irregularity (missed, mistimed or reduced a basal insulin dose) in the previous 30 days. Up to 60% reported risk for hypoglycemia as the reason for intentional dosing irregularities. Of all patients, 80% reported experiencing a self-treated hypoglycemic event, and 33% recalled having at least 1 event in the previous month. HCPs recorded similar levels of patient-reported dosing irregularities. Over 90% indicated they recommended patients to temporarily reduce their insulin doses to deal with hypoglycemia. CONCLUSIONS: A sizeable minority of patients experienced dosing irregularities and self-treated hypoglycemia in this Canadian cohort. The data suggest that HCPs who completed the survey are aware of this and of the need to provide education and support for patients who regularly miss, mistime or reduce insulin doses. Although the desire to prevent hypoglycemic events is understandable and important, HCPs need to ensure fear of hypoglycemia does not compromise optimal diabetes management.

Acute management and outcomes of patients with diabetes mellitus presenting to Canadian emergency departments with hypoglycemia.

OBJECTIVES: This retrospective chart audit examined the demographics, investigations, management and outcomes of adult patients with diabetes mellitus presenting to Canadian emergency departments (EDs). METHODS: All sites conducted a search of their electronic medical records using International Classification of Diseases, Tenth Revision, codes to identify ED visits for hypoglycemia between 2008 and 2010. Patient characteristics, demographics, ED management, ED resources and outcome are reported. RESULTS: A total of 1039 patients over the age of 17 years were included in the study; 347 (33.4%) were classified as type 1 diabetes and 692 (66.6%) were classified as type 2 diabetes. Type 2 diabetes patients were significantly older (73 vs. 49 years; p<0.0001) and had more chronic conditions recorded on their chart (all p<0.001). Most subjects arrived by ambulance, and triage scores revealed severe presentations in 39% of cases. Treatments for hypoglycemia were common (75.7%) during prehospital transport; 38.5% received intravenous glucose and 40.1% received glucagon. Hypoglycemia treatments in the ED included oral (76.8%), intravenous (29.6%) and continuous infusion (27.7%) of glucose. Diagnostic testing (81.9%) commonly included electrocardiograms (51.9%), chest radiography (37.5%) and head computed tomography scans (14.5%). Most patients (73.5%) were discharged; however, more subjects with type 2 diabetes required admission (30.3 vs. 8.8%). Discharge instructions were documented in only 55.5% of patients, and referral to diabetes services occurred in fewer than 20% of cases. Considerable variation existed in the management of hypoglycemia across EDs. CONCLUSIONS: Patients with diabetes presenting to an ED with hypoglycemia consume considerable healthcare resources, and practice variation exists. Emergency departments should develop protocols for the management of hypoglycemia, with attention to discharge planning to reduce recurrence.

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test.

OBJECTIVE: IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes. METHODS: In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed. RESULTS: At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC0-4h) than insulin degludec (estimated treatment difference [ETD] -12.79 mg/dl [95% CI: -21.08; -4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD -1.62 mg/dl [95% CI: -10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -6.13 mg/dl [95% CI: -10.27, -1.98], P = .0047) and similar reductions versus liraglutide (ETD -1.80 mg/dl [95% CI: -2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively). CONCLUSIONS: Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.

New Insulins and New Aspects in Insulin Delivery.

The major abnormality in both type 1 and type 2 diabetes is insulin deficiency. The methods of replacing insulin have improved throughout the decades, but hypoglycemia is still the limiting factor for many individuals with diabetes, and it prevents them from achieving ideal glycemic targets. New insulin and newer delivery systems are being developed that can improve some of the limitations of current insulins or make the delivery of insulins more acceptable for some patients. Extending the duration of action of basal insulins and shortening the peak of fast-acting insulins may have advantages for individuals with diabetes. Different delivery systems may make insulin more acceptable to patients and may have other advantages, which may aid in attaining better glycemic control.

Acute management and outcomes of patients with diabetes mellitus presenting to Canadian emergency departments with hypoglycemia.

OBJECTIVES: This retrospective chart audit examined the demographics, investigations, management and outcomes of adult patients with diabetes mellitus presenting to Canadian emergency departments (EDs). METHODS: All sites conducted a search of their electronic medical records using International Classification of Diseases, Tenth Revision, codes to identify ED visits for hypoglycemia between 2008 and 2010. Patient characteristics, demographics, ED management, ED resources and outcome are reported. RESULTS: A total of 1039 patients over the age of 17 years were included in the study; 347 (33.4%) were classified as type 1 diabetes and 692 (66.6%) were classified as type 2 diabetes. Type 2 diabetes patients were significantly older (73 vs. 49 years; p<0.0001) and had more chronic conditions recorded on their chart (all p<0.001). Most subjects arrived by ambulance, and triage scores revealed severe presentations in 39% of cases. Treatments for hypoglycemia were common (75.7%) during prehospital transport; 38.5% received intravenous glucose and 40.1% received glucagon. Hypoglycemia treatments in the ED included oral (76.8%), intravenous (29.6%) and continuous infusion (27.7%) of glucose. Diagnostic testing (81.9%) commonly included electrocardiograms (51.9%), chest radiography (37.5%) and head computed tomography scans (14.5%). Most patients (73.5%) were discharged; however, more subjects with type 2 diabetes required admission (30.3 vs. 8.8%). Discharge instructions were documented in only 55.5% of patients, and referral to diabetes services occurred in fewer than 20% of cases. Considerable variation existed in the management of hypoglycemia across EDs. CONCLUSIONS: Patients with diabetes presenting to an ED with hypoglycemia consume considerable healthcare resources, and practice variation exists. Emergency departments should develop protocols for the management of hypoglycemia, with attention to discharge planning to reduce recurrence.

Dosing irregularities and self-treated hypoglycemia in type 2 diabetes: results from the Canadian cohort of an international survey of patients and healthcare professionals.

OBJECTIVE: Despite their importance in achieving good glycemic control, few real-world data on insulin dosing irregularities and hypoglycemia are available. The multinational, online Global Attitude of Patients and Physicians (GAPP2) survey was conducted to address this situation. METHODS: Insulin-treated patients with type 2 diabetes and healthcare professionals (HCPs) who treat such patients were surveyed in an online cross-sectional study. This article summarizes findings from a sample of the online population in a Canadian cohort of 156 patients and 202 HCPs. RESULTS: A total of 156 patients completed the questionnaires; 26% reported experiencing a dosing irregularity (missed, mistimed or reduced a basal insulin dose) in the previous 30 days. Up to 60% reported risk for hypoglycemia as the reason for intentional dosing irregularities. Of all patients, 80% reported experiencing a self-treated hypoglycemic event, and 33% recalled having at least 1 event in the previous month. HCPs recorded similar levels of patient-reported dosing irregularities. Over 90% indicated they recommended patients to temporarily reduce their insulin doses to deal with hypoglycemia. CONCLUSIONS: A sizeable minority of patients experienced dosing irregularities and self-treated hypoglycemia in this Canadian cohort. The data suggest that HCPs who completed the survey are aware of this and of the need to provide education and support for patients who regularly miss, mistime or reduce insulin doses. Although the desire to prevent hypoglycemic events is understandable and important, HCPs need to ensure fear of hypoglycemia does not compromise optimal diabetes management.