Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla‐100) or insulin detemir (DET) with ≥1 A1C measurement during 12‐month baseline and 18‐month follow‐up periods were included. Patients with a refill gap of >90 days were considered non‐persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow‐up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non‐persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.     

Combination of oral antidiabetic agents with basal insulin versus premixed insulin alone in randomized elderly patients with type 2 diabetes mellitus

OBJECTIVES: To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs. DESIGN: A 24-week, multicenter, open, randomized (1:1), parallel study. SETTING: Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice-daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (or=6.7 mmol/L) and hemoglobin (Hb)A(1c) levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63). MEASUREMENTS: HbA(1c), FBG, hypoglycemia, insulin dose, and adverse events were recorded. RESULTS: HbA(1c) decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA(1c) decrease for glargine+OAD and 70/30 was -1.9% and -1.4%, respectively (P=.003). More patients reached HbA(1c) of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (-57 mg/dL (-3.2 mmol/L)) than with 70/30 (-40 mg/dL (-2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient-year) than did those treated with 70/30 (9.09/patient-year) (P=.008). CONCLUSION: In elderly patients, addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone.     

Options for the intensification of insulin therapy when basal insulin is not enough in type 2 diabetes mellitus

In the early treatment of type 2 diabetes mellitus (T2DM), the addition of a basal insulin, such as insulin glargine, to existing oral therapy can help patients attain recommended glycaemic control targets, including haemoglobin A_1c (HbA_1c) <7% and fasting blood glucose <5.5 mmol/l (<100 mg/dl). For patients close to but not at target, the management of postprandial glucose excursions with a rapid-acting insulin, such as insulin glulisine, can provide further improvements in glycaemic control. In this review, the options for intensifying insulin therapy with the addition of one or more daily doses of prandial insulin are discussed. In addition, the advantages/disadvantages of choosing a basal–bolus vs. a premixed insulin strategy are discussed. A conceptually simple approach for the treatment of T2DM is for optimization of the basal insulin dose (added to oral antidiabetic drugs) to target fasting glycaemia followed by the addition of a single prandial dose of rapid-acting insulin to target the largest glucose excursion. A second and third dose of prandial insulin can then be added if HbA_1c remains above target and to manage postprandial glucose excursions at other meals. Prospective studies are underway to further examine this concept and determine the benefit of this approach not only on overall glycaemic control but also on cardiovascular risk.     

Differences in insulin treatment satisfaction following randomized addition of biphasic,prandial or basal insulin to oral therapy in type 2 diabetes

Aim: No differences in patient health status as measured by the EuroQol‐5 Dimension (EQ‐5D) questionnaire were observed at 1 year between groups randomized to addition of biphasic, prandial or basal insulin to oral therapy in the treat‐to‐target in type 2 diabetes trial. We further investigated insulin treatment satisfaction between groups. Methods: Seven hundred and eight patients with suboptimal glycated haemoglobin levels (7.0–10.0%) taking maximally tolerated doses of metformin and sulphonylurea were randomized to biphasic insulin aspart twice‐daily, prandial insulin aspart three times daily or basal insulin detemir once‐daily (twice if required). At 1 year self‐completed Insulin Treatment Satisfaction Questionnaires (ITSQ) were administered. Lower scores indicated lower treatment satisfaction. We tested for differences between the three groups for the ITSQ total score and for each of the five ITSQ domain scores adjusting for age, gender, ethnicity and education. Results: All 22 ITSQ subscales were completed by 554 (78.2%) patients. Their mean (s.d.) age was 61.5 (9.4) years, body weight 86.1 (16) kg and median (IQR) diabetes duration 9 (6–13) years. Sixty‐five percent (358) were male. Median (IQR) 1‐year ITSQ total score was lower in patients allocated to prandial therapy (76.5, 68.0–88.6) than in patients allocated to biphasic insulin (83.3, 74.2–90.2) or basal insulin (84.1, 73.5–93.2). With the exception of ‘perceived glycaemic control’, 1‐year adjusted ITSQ scores were significantly different between groups for each of the ITSQ domains, with lower scores for prandial insulin compared with the basal or biphasic groups. Median (IQR) ITSQ scores were lower in patients with a gain in body mass index (BMI) > 1.23 kg/m² over 1 year (79.5, 69.7–89.4) compared to those with a lesser or no gain in BMI (84.1, 74.2–92.4) and in those with occurrence of hypoglycaemia (79.5, 69.7–88.6) compared to those with no hypoglycaemia (84.1, 73.7–93.2). Conclusion: Specific measurement of insulin treatment satisfaction identifies differences between regimens used to intensify treatment for type 2 diabetes. Impact of treatment on lifestyle needs to be considered as a factor in the choice of an insulin regimen.     

First insulinization with basal insulin in patients with Type 2 diabetes in a real-world setting in Asia

Background: The First Basal Insulin Evaluation (FINE) Asia study is a multinational, prospective, observational study of insulin‐naïve Type 2 diabetes mellitus (T2DM) patients in Asia, uncontrolled (A1c ≥ 8%) on oral hypoglycemic agents, designed to evaluate the impact of basal insulin initiation. Methods: Basal insulin was initiated with or without concomitant oral therapy and doses were adjusted individually. All treatment choices, including the decision to initiate insulin, were at the physician’s discretion to reflect real‐life practice. Results: Patients (n = 2679) from 11 Asian countries were enrolled (mean [±SD] duration of diabetes 9.3 ± 6.5 years; weight 68.1 ± 12.7 kg; A1c 9.8 ± 1.6%). After 6 months of basal insulin (NPH insulin, insulin glargine, or insulin detemir), A1c decreased to 7.7 ± 1.4%; 33.7% patients reached A1c <7%. Fasting blood glucose (FBG) decreased from 11.7 ± 3.6 to 7.2 ± 2.5 mmol/L and 36.8% of patients reached FBG <6.1 mmol/L. The mean daily insulin dose prescribed increased marginally from 0.18 to 0.23 U/kg per day at baseline to 0.22–0.24 U/kg per day at Month 6. Mean changes in body weight and reported rates of hypoglycemia were low over the duration of the study. Conclusions: Initiation of insulin therapy is still being delayed by approximately 9 years, resulting in many Asian patients developing severe hyperglycemia. Initiating insulin treatment with basal insulin was effective and safe in Asian T2DM patients in a real‐world setting, but insulin needs may differ from those in Western countries.     

Prevention of weight gain in type 2 diabetes requiring insulin treatment

Background: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds.
Aim: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin.
Methods: In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1–2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control.
Results: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 ± 0.3 mg/day (mean ± standard error of the mean), and a total daily insulin dose of 24.1 ± 2.6 IU. Fasting glucose levels decreased from 12.7 ± 0.6 mmol/l to 8.1 ± 0.3 mmol/l (p  <  0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 ± 0.4 to 7.7 ± 0.2% (p  <  0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 ± 3.6 kg vs. 85.7 ± 3.3 kg, p = 0.99).
Conclusion: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.     

Optimum management of type 2 diabetes – timely introduction, optimization and intensification of basal insulin

The natural progression of type 2 diabetes mellitus (T2DM) requires continuing medical care, early insulin intensification and patient self-management education to reduce the risk of long-term complications, including microvascular and macrovascular complications. However, too few people are on insulin, and all too commonly have poor glycaemic control. This paradigm significantly increases the risk for long-term complications. It is becoming increasingly apparent that the early introduction of basal insulin, such as insulin glargine, is essential to provide clinically important improvements in glycaemic control. In this review, we discuss the rationale for the earlier insulinization in T2DM in order to reach and maintain treatment targets and to provide further support for the recent American Diabetes Association and European Association for the Study of Diabetes consensus statement.     

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

Aims/Introduction

Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients.

Materials and Methods

The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed.

Results

Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy.

Conclusions

Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.     

Fructose and insulin sensitivity in patients with type 2 diabetes

Abstract. The effect of dietary fructose (20% of carbohydrate calories, 45–65 g day^?1 for 4 weeks) on glycaemic control, serum lipid, lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients. The study was done in a randomized, double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day. The patients were hospitalized throughout the study periods. The fasting plasma glucose concentration decreased during the fructose (from 10.7 ± 1.4 mmol l^?1 to 8.0 ± 0.8 mmol l^?1, P < 0.02) and the control diet (from 10.1 ± 0.9 mmol l^?1 to 8.0 ± 0.7 mmol l^?1 P < 0.05). The mean diurnal blood glucose concentration also fell both during the fructose (from 10.8± 0.5 mmol l^?1 to 8.4 ± 0.3 mmol l^?1, P < 0.001) and the control diet (from 10.3 ± 0.3 mmol l^?1 to 8.8 ± 0.9 mmol l^?1, P < 0.01). The HbA₁ concentration improved (P < 0.02) only during the fructose diet. Insulin sensitivity increased by 34% (P < 0.05) during the fructose diet, but remained unchanged during the control period. Serum insulin, triglyceride, apoprotein A-I and A-II concentrations, body weight, blood pressure and blood lactate remained unchanged during both diets. In conclusion, substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes.     

A comparison of insulin aspart and regular insulin in elderly patients with type 2 diabetes

AIM: To evaluate the pharmacokinetic and pharmacodynamic properties of insulin aspart in elderly patients with diabetes. METHODS: Studies were conducted in elderly patients with diabetes (n = 19, M/F 10/9, age 72 +/- 1 years, BMI 27 +/- 1 kg/m(2), HbA(1c) 6.4 +/- 0.1%, diabetes duration < 5 years). Nine patients were treated with metformin, and ten with diet. Subjects underwent 2 studies in random order. In one study, 0.1 u/kg of novolin R (Novo Nordisk, Copenhagen, Denmark) was administered at 7:30 am. Thirty minutes later, at time 0, subjects were given 235 ml of ensure with fibre. The other study was identical to the first except that insulin aspart (Novorapid, Novo Nordisk, Copenhagen, Denmark) 0.1 u/kg was given at time zero. Insulin and glucose valuves were measured as at regular intervals. RESULTS: Insulin and glucose profiles were nearly identical with insulin aspart and regular human insulin. The AUC for glucose (aspart: 6.9 +/- 0.1 mM; regular: 7.1 +/- 0.1 mM, p = ns) and insulin (aspart: 335 +/- 30 pM; regular: 330 +/- 25 pM, p = ns) did not differ between groups. CONCLUSIONS: Insulin aspart appears to act similarly to regular human insulin in elderly patients with type 2 diabetes.     

Analysis of patient satisfaction with a prefilled insulin injection device in patients with type 1 and type 2 diabetes

In this issue of Journal of Diabetes Science and Technology, Hancu and colleagues present an observational 6-8-week Pan-European and Canadian prospective survey on patient satisfaction with a prefilled insulin injection device, the SoloSTAR pen device, in patients with type 1 and 2 diabetes (n = 6542). The SoloSTAR pen is one of several up-to-date insulin pens of high quality and characteristics that fit many of our patients with diabetes. The mainly excellent-good votes of the participants for the SoloSTAR are not surprising, as we have seen continuous improvements with prefilled pens, such as the SoloSTAR device. Several years ago, patients as well as health care providers found considerable differences between the available pen options. Nowadays, as almost all pen providers have clearly improved their products, the differences are much smaller; we are closer to a "perfect" prefilled pen device. Nevertheless, there is a need for more randomized controlled trials, ideally sponsored not by just one manufacturer, to be able to make clear statements toward different pen device aspects (e.g., accuracy of dosing, adherence to therapy, ease of use, and patient satisfaction). An additional handicap is the difficulty to get blinded study designs.