Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus.

Many people with type 2 diabetes mellitus (T2DM) fail to achieve glycaemic control promptly after diagnosis and do not receive timely treatment intensification. This may be in part due to 'clinical inertia', defined as the failure of healthcare providers to initiate or intensify therapy when indicated. Physician-, patient- and healthcare-system-related factors all contribute to clinical inertia. However, decisions that appear to be clinical inertia may, in fact, be only 'apparent' clinical inertia and may reflect good clinical practice on behalf of the physician for a specific patient. Delay in treatment intensification can happen at all stages of treatment for people with T2DM, including prescription of lifestyle changes after diagnosis, introduction of pharmacological therapy, use of combination therapy where needed and initiation of insulin. Clinical inertia may contribute to people with T2DM living with suboptimal glycaemic control for many years, with dramatic consequences for the patient in terms of quality of life, morbidity and mortality, and for public health because of the huge costs associated with uncontrolled T2DM. Because multiple factors can lead to clinical inertia, potential solutions most likely require a combination of approaches involving fundamental changes in medical care. These could include the adoption of a person-centred model of care to account for the complex considerations influencing treatment decisions by patients and physicians. Better patient education about the progressive nature of T2DM and the risks inherent in long-term poor glycaemic control may also reinforce the need for regular treatment reviews, with intensification when required.

Differential effects of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide and metformin on pancreatic ß-cell and insulin sensitivity during a standardized test meal in patients with type 2 diabetes.

This substudy of the AWARD-3 trial evaluated the effects of the once-weekly glucagon-like peptide-1 receptor agonist, dulaglutide, versus metformin on glucose control, pancreatic function and insulin sensitivity, after standardized test meals in patients with type 2 diabetes. Meals were administered at baseline, 26 and 52 weeks to patients randomized to monotherapy with dulaglutide 1.5 mg/week (n = 133), dulaglutide 0.75 mg/week (n = 136), or metformin ≥1500 mg/day (n = 140). Fasting and postprandial serum glucose, insulin, C-peptide and glucagon levels were measured up to 3 h post-meal. ß-cell function and insulin sensitivity were assessed using empirical variables and mathematical modelling. At 26 weeks, similar decreases in area under the curve for glucose [AUCglucose (0-3 h)] were observed among all groups. ß-cell function [AUCinsulin /AUCglucose (0-3 h)] increased with dulaglutide and was unchanged with metformin (p ≤ 0.005, both doses). Dulaglutide improved insulin secretion rate at 9 mmol/l glucose (p ≤ 0.04, both doses) and ß-cell glucose sensitivity (p = 0.004, dulaglutide 1.5 mg). Insulin sensitivity increased more with metformin versus dulaglutide. In conclusion, dulaglutide improves postprandial glycaemic control after a standardized test meal by enhancing ß-cell function, while metformin exerts a greater effect on insulin sensitivity.

Early fasting glucose measurements can predict later glycaemic response to once weekly dulaglutide.

AIMS: To assess whether early measures of fasting blood glucose predict later glycaemic response with once-weekly dulaglutide in patients with Type 2 diabetes mellitus. METHODS: Post hoc analyses were conducted separately for two phase 3 studies (AWARD-5 and AWARD-1) in patients assigned to once-weekly dulaglutide. Week 2 fasting blood glucose was used as a predictor variable, and glycaemic treatment response was defined by HbA1c response based on a composite efficacy endpoint. The association between fasting blood glucose and the glycaemic response was analysed using chi-square tests. RESULTS: There was a strong association between fasting blood glucose < 7.9 mmol/l at week 2 and achieving the HbA1c composite efficacy endpoint at week 26 (P < 0.01). Higher fasting blood glucose at week 2, however, did not predict absence of glycaemic response and requires further assessment. CONCLUSIONS: Fasting blood glucose measured at 2 weeks may be an early and useful predictor of glycaemic response to once-weekly dulaglutide treatment.

Treatment satisfaction in people with type 2 diabetes mellitus treated with once-weekly dulaglutide: data from the AWARD-1 and AWARD-3 clinical trials.

AIMS: To compare treatment satisfaction among people with type 2 diabetes receiving dulaglutide 1.5 mg and dulaglutide 0.75 mg (a once-weekly, long-acting, glucagon-like peptide-1 receptor agonist) with those receiving either exenatide or placebo (AWARD-1 study) or metformin (AWARD-3 study) over 52 weeks. METHODS: The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and change version (DTSQc) were used to evaluate total treatment satisfaction and perceived frequency of hyperglycaemia and hypoglycaemia. RESULTS: In the AWARD-1 study, significant improvements from baseline were observed in total DTSQs score for both dulaglutide doses (26 and 52 weeks) and exenatide (26 weeks). The improvement was significantly greater with both dulaglutide doses compared with placebo (26 weeks) and exenatide (26 and 52 weeks). The perceived frequency of hyperglycaemia was lower for all groups at 26 and 52 weeks compared with baseline. The improvement was greater with both dulaglutide doses and exenatide compared with placebo at 26 weeks, and was also greater with both dulaglutide doses compared with exenatide at 26 and 52 weeks. The exenatide group had an increase in perceived frequency of hypoglycaemia at 26 and 52 weeks. In the AWARD-3 study, significant improvements from baseline were observed for total DTSQs scores in all groups at 26 and 52 weeks. Perceived frequency of hyperglycaemia was lower for all groups at 26 and 52 weeks compared with baseline, and this improvement was greater with both dulaglutide doses compared with metformin at 52 weeks. CONCLUSIONS: Dulaglutide was associated with improvements in treatment satisfaction and a decrease in perceived frequency of hyperglycaemia.