Luigi Meneghini

Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study

Diabet. Med. 29, 682–689 (2012)

The Efficacy and Safety of Insulin Degludec Given in Variable Once-Daily Dosing Intervals Compared With Insulin Glargine and Insulin Degludec Dosed at the Same Time Daily: A 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes

OBJECTIVE The requirement to inject current basal insulin analogs at a fixed time each day may complicate adherence and compromise glycemic control. This trial evaluated the efficacy and safety of varying the daily injection time of insulin degludec (IDeg), an ultra-long-acting basal insulin. RESEARCH DESIGN AND METHODS This 26-week, open-label, treat-to-target trial enrolled adults (≥18 years) with type 2 diabetes who were either insulin naïve and receiving oral antidiabetic drugs (OADs) (HbA1c = 7–11%) or previously on basal insulin ± OAD(s) (HbA1c = 7–10%). Participants were randomized to 1) once-daily (OD) IDeg in a prespecified dosing schedule, creating 8–40-h intervals between injections (IDeg OD Flex; n = 229); 2) once-daily IDeg at the main evening meal (IDeg OD; n = 228); or 3) once-daily insulin glargine at the same time each day (IGlar OD; n = 230). The primary outcome was noninferiority of IDeg OD Flex to IGlar OD in HbA1c reduction after 26 weeks. RESULTS After 26 weeks, IDeg OD Flex, IDeg OD, and IGlar OD improved HbA1c by 1.28, 1.07, and 1.26% points, respectively (estimated treatment difference [IDeg OD Flex − IGlar OD]: 0.04% points [–0.12 to 0.20], confirming noninferiority). No statistically significant differences in overall or nocturnal hypoglycemia were found between IDeg OD Flex and IGlar OD. Comparable glycemic control and rates of hypoglycemia were seen with IDeg OD Flex and IDeg OD. Adverse event profiles were similar across groups. CONCLUSIONS The use of extreme dosing intervals of 8–40 h demonstrates that the daily injection time of IDeg can be varied without compromising glycemic control or safety.

Insulin Degludec in Type 1 Diabetes: A randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine

OBJECTIVE Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes. RESEARCH DESIGN AND METHODS In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m2) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes. RESULTS At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52–1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65–1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25–0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44–1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments. CONCLUSIONS In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.

The usage of a simplified self‐titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE™ 303 study

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVE™ 303) Study (n = 5604) evaluated the effectiveness of insulin detemir, a long‐acting basal insulin analogue, using a simplified patient self‐adjusted dosing algorithm (303 Algorithm group) compared with standard‐of‐care physician‐driven adjustments (Standard‐of‐care group) in a predominantly primary care setting, over a period of 6 months. Insulin detemir was to be started once‐daily as add‐on therapy to any other glucose‐lowering regimens or as a replacement of prestudy basal insulin in patients with type 2 diabetes. Investigator sites rather than individual patients were randomized to either the 303 Algorithm group or the Standard‐of‐care group. Patients from the 303 Algorithm group sites were instructed to adjust their insulin detemir dose every 3 days based on the mean of three ‘adjusted’ fasting plasma glucose (aFPG) values (capillary blood glucose calibrated to equivalent plasma glucose values) using a simple algorithm: mean aFPG < 80 mg/dl (<4.4 mmol/l), reduce dose by 3 U; aFPG between 80 and 110 mg/dl (4.4–6.1 mmol/l), no change; and aFPG > 110 mg/dl (>1.1 mmol/l), increase dose by 3 U. The insulin detemir dose for patients in the Standard‐of‐care group was adjusted by the investigator according to the standard of care. Mean A1C decreased from 8.5% at baseline to 7.9% at 26 weeks for the 303 Algorithm group and from 8.5 to 8.0% for the Standard‐of‐care group (p = 0.0106 for difference in A1C reduction between the two groups). Mean FPG values decreased from 175 mg/dl (9.7 mmol/l) at baseline to 141 mg/dl (7.8 mmol/l) for the 303 Algorithm group and decreased from 174 mg/dl (9.7 mmol/l) to 152 mg/dl (8.4 mmol/l) for the Standard‐of‐care group (p < 0.0001 for difference in FPG reduction between the two groups). Mean body weight remained the same at 26 weeks in both groups (change from baseline 0.1 and −0.2 kg for the 303 Algorithm group and the Standard‐of‐care group respectively). At 26 weeks, 91% of the patients in the 303 Algorithm group and 85% of the patients in the Standard‐of‐care group remained on once‐daily insulin detemir administration. The rates of overall hypoglycaemia (events/patient/year) decreased significantly from baseline in both groups [from 9.05 to 6.44 for the 303 Algorithm group (p = 0.0039) and from 9.53 to 4.95 for the Standard‐of‐care group (p < 0.0001)]. Major hypoglycaemic events were rare in both groups (0.26 events/patient/year for the 303 Algorithm group and 0.20 events/patient/year for the Standard‐of‐care group; p = 0.2395). In conclusion, patients in the 303 Algorithm group achieved comparable glycaemic control with higher rate of hypoglycaemia as compared with patients in the Standard‐of‐care group, possibly because of more aggressive insulin dose adjustments. The vast majority of the patients in both groups were effectively treated with once‐daily insulin detemir therapy. The use of insulin detemir in this predominantly primary care setting achieved significant improvements in glycaemic control with minimal risk of hypoglycaemia and no weight gain.

An Electronic Case Manager for Diabetes Control

OBJECTIVE To evaluate the usage and safety of an electronic case manager (ECM) system designed to facilitate the task of glycemic control. Sustained improvement in blood glucose control is the proven treatment outcome that will reduce or eliminate the long-term complications of diabetes. RESEARCH DESIGN AND METHODS A customized microcomputer system served as the ECM. Located at the clinic, this voice-interactive system required the remote patient to need only a touch-tone telephone. Patients accessed the system to report daily selfmeasured glucose levels or hypoglycemic symptoms together with associated lifestyle events. System beta-testing was in an open-case series (n = 184) in an academic diabetes center with the goal of evaluating the ECM in terms of utilization, frequency of crises, and fiscal matters. RESULTS Of the patients, 58% (n = 107) actively used the ECM for their daily diabetes care, accumulating 788 patient-months of follow-up. Over 45,000 telephone calls were received by the ECM during the start-up year. Each call was processed instantly and automatically. Patients benefited from having 24-h access to the ECM. Prevalence of diabetes-related crises (hyperglycemia =400 mg/dl [22 mmol/1] or hypoglycemia <50 mg/dl [2.8 mmol/1]) decreased approximately threefold (P < 0.05), with a concomitant statistically significant decrease in HbA1c of 0.8% at 6 months (n = 45, P = 0.024) and 0.9% at 12 months (n = 30, P = 0.044). The ECM provided 24-h on-line assistance in adjusting daily insulin and/or tablet therapy, automatic generation of standardized medical reports, electronic medical-legal documentation, as well as a marked reduction in the time spent on the phone with patients. Clinic visits in managing complex diabetes were reduced approximately twofold (P < 0.0001), and the effort spent by case managers was estimated. CONCLUSIONS Patients with diabetes who accessed the ECM system received timely, cost-effective, and reliable medical intervention. This reduced the incidence of diabetic crises and the need for frequent clinic visits. The ECM empowers case managers to provide safer and superior diabetes care.

Obesity, bariatric surgery and type 2 diabetes—a systematic review

Obesity is endemic in the United States and is closely linked to the development of type 2 diabetes. Both obesity and diabetes are responsible for significant morbidity and mortality. Likewise, both conditions are resistant to treatment. Recent studies have evaluated prevention of type 2 diabetes through intensive lifestyle intervention, while others are examining the impact of bariatric surgery on type 2 diabetes. This article presents an overview of the impact of bariatric surgical and lifestyle interventions on the prevention and treatment of type 2 diabetes. Although studies using a variety of bariatric surgical techniques are included, the focus is on two interventions in particular: the Roux‐en‐Y gastric bypass and the laparoscopic silicone gastric banding procedure. Outcomes of these procedures are further contrasted with recent lifestyle intervention studies, in particular, the Diabetes Prevention Program study. Gastric bypass studies have been associated with a 99 to 100% prevention of diabetes in patients with IGT and an 80 to 90% clinical resolution of diagnosed early type 2 diabetes. Gastric banding procedures are associated with a lower median (50–60%) clinical remission of type 2 diabetes. Lifestyle intervention studies of obese and glucose‐intolerant patients have achieved a 50% reduction in the progression of IGT to diabetes over the short term, with no reported resolution of the disease. Weight loss by any means in the obese patient appears to prevent progression to type 2 diabetes, at least in the short term. Furthermore, sustained weight loss through bariatric surgical intervention is associated both with prevention of progression of IGT and with clinical remission of early type 2 diabetes. Copyright

Insulin detemir improves glycaemic control without weight gain in insulin-naive patients with type 2 diabetes : subgroup analysis from the PREDICTIVE™ study

Objective: Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVETM) is a multi‐national, open‐label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. This post hoc subanalysis evaluates insulin‐naïve patients on oral antidiabetic drugs (OADs) who were initiated on insulin detemir as basal therapy (± OADs).

Efficacy and safety of ezetimibe co‐administered with simvastatin in thiazolidinedione‐treated type 2 diabetic patients

Aim:  In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low‐density lipoprotein cholesterol (LDL‐C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose‐lowering properties and their modest beneficial effects on triglycerides (TG) and high‐density lipoprotein cholesterol (HDL‐C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid‐modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD‐treated T2DM patients.

Factors associated with injection omission/non‐adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study

To examine factors associated with insulin injection omission/non‐adherence on a global basis.

Study of Once Daily Levemir (SOLVE™): Insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice

Aims: The aim of this analysis is to determine the timing of insulin initiation in routine clinical practice, especially in relation to glycaemic control and use of oral antidiabetic drugs (OADs).