Safety and Efficacy of Combination Therapy with Insulin Glargine and Oral Hypoglycaemic Agents Including DPP-4 Inhibitors in Japanese T2DM Patients: ALOHA 2 Study, a Post-Marketing Surveillance for Lantus^®

Aims: In the Add-on Lantus®?to Oral Hypoglycaemic Agents 2 (ALOHA 2) Study in Japanese adults with type 2 diabetes mellitus (T2DM), data on the safety and efficacy of combination therapy with insulin glargine (Lantus®) and oral anti-hyperglycaemic drugs (OADs) including dipeptidyl peptidase-4 (DPP-4) inhibitors in a real-life setting were collected and analyzed. Methods: This postmarketing surveillance was a prospective, observational, 24-week study that complied with the pharmaceutical affairs law and the ministerial ordinance of “Good Post-Marketing Study Practice (GPSP)” in Japan. Safety, efficacy and patient-reported outcomes (PROs);patients’ satisfaction with treatment (DTSQs and DTSQc) and patients’ self-reported health (EQ-5D and EQ-VAS) of combination therapy of insulin glargine and OADs were evaluated. Results: A total of 2,630 patients were enrolled. Of the 2,602 patients in the safety analysis population, 161 patients experienced 175 cases of adverse drug reactions, and the major adverse drug reaction was hypoglycaemia (140 patients, 5.38%). Out of those with hypoglycaemia, 11 patients (0.42%) had severe hypoglycaemia and the incidence rate (episodes per patient-year) was 0.019. Basal supported oral therapy (BOT) with insulin glargine substantially reduced the HbA1c, FPG and 2 hour-PPG levels for 24 weeks by -1.61%, -54.4 mg/dL and -74.5 mg/dL respectively. The mean weight was increased, however the change was +0.50 kg. In addition, the treatment satisfaction scores of DTSQs (mean treatment satisfaction score increased 3.6 from baseline to last observation) and DTSQc, EQ-5D index scores and EQ-VAS scores were significantly improved. Conclusion: Insulin glargine and OADs combination therapy was suggested to be effective and well tolerated. Patients’ satisfaction with treatment and their self-reported health improved in spite of the addition of injections to oral agents. The combination therapy of insulin glargine and OADs including DPP-4 inhibitors is likely to be considered an important therapeutic option in the diabetic patients.

Multicenter Survey of the Isometric Lower Extremity Strength in Patients with Type 2 Diabetes (MUSCLE-std): Design and Study Protocol

Background: The lower extremity muscle strength has been shown to be weaker in patients with diabetes mellitus, primarily due to the effects of diabetic polyneuropathy, a common diabetic complication. With respect to assessments of the lower extremity muscle strength, reference values for the knee extension force in healthy Japanese subjects have been reported. The clinical significance of applying knee extension force in the assessment of efficacy of exercise therapy and patient education has also been demonstrated, and the use of an individualized approach in physical exercise based on the quantitative assessment of the lower extremity muscle strength is becoming one of the most important strategies for promoting effective rehabilitation. Methods: The study is a multicenter, cross-sectional investigation. We will measure the knee extension force and evaluate the diabetic polyneuropathy in patients with type 2 diabetes using uniform equipment and methodology at all centers. We will compare the knee extension force between the subjects with and without diabetic polyneuropathy and will investigate the associations between the knee extension force and both glycemic control and exercise habits. The trial registration is UMIN CTR (UMIN000002810). Discussion: The lower extremity muscle strength has been insufficiently investigated in Japanese patients with diabetes. This study was designed to establish reference values for the knee extension force in Japanese diabetic patients with and without diabetic polyneuropathy.