Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study.

AIMS: To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone. METHODS: This was a multi-centre, phase 3, randomized, double-blind, placebo-controlled study comparing linagliptin 5 mg once daily (n = 183) and placebo (n = 89) as add-on to metformin and pioglitazone. The primary endpoint was the change from baseline in glycated haemoglobin (HbA1c ) after 24 weeks. RESULTS: The placebo-corrected adjusted mean (se) change in HbA1c from baseline to 24 weeks was -6 (1) mmol/mol [-0.57 (0.13)%] (P < 0.0001). In patients with baseline HbA1c ≥ 53 mmol/mol (7.0%), 32.4% of patients in the linagliptin group and 13.8% in the placebo group achieved HbA1c < 53 mmol/mol (7.0%) (odds ratio 2.94; P = 0.0033). The placebo-corrected adjusted mean (se) change from baseline in fasting plasma glucose at week 24 was -0.57 (0.26) mmol/l [-10.4 (4.7) mg/dl] (P = 0.0280). The incidence of serious adverse events was 2.2% with linagliptin and 3.4% with placebo. Investigator-defined hypoglycaemia occurred in 5.5% of the linagliptin group and 5.6% of the placebo group. No meaningful changes in mean body weight were noted for either group. CONCLUSIONS: Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control, without an additional risk of hypoglycaemia or weight gain (Clinical Trials Registry No: NCT 00996658).

Dose response and safety of telmisartan in patients with mild to moderate hypertension.

This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension (diastolic blood pressure [DBP] 100 to 114 mmHg). After a 28-day placebo run-in period, patients were randomized to 28 days of once-daily, double-blind, double-dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo. Blood pressure (BP) was manually recorded for 12 hours after the first dose and after 24 hours at baseline (Day 0), Day 1, and Day 28 of double-blind treatment. Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations. All doses of telmisartan and enalapril significantly reduced BP compared with placebo (p < or = 0.01). Mean +/- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 +/- 1.3 mmHg and 9.8 +/- 1.3 mmHg in the telmisartan groups, 9.6 +/- 1.3 mmHg with enalapril, and 1.5 +/- 1.3 mmHg with placebo. Mean +/- SE reductions in supine systolic blood pressure (SBP) were between 10.0 +/- 2.2 mmHg and 15.5 +/- 2.2 mmHg with telmisartan versus 10.2 +/- 2.1 mmHg with enalapril; placebo increased supine SBP by 3.5 +/- 2.1 mmHg. The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril. No significant linear trend in BP reduction was evident among telmisartan doses. Reductions in SBP and DBP were maintained over the 24-hour period at Day 28. Treatment did not affect supine heart rate. Trough/peak DBP ratios were > or = 85% for all telmisartan doses versus 65% for enalapril. High interpatient variability in telmisartan plasma concentrations was observed. For example, mean +/- SD values for Cmax were 159 +/- 104 ng/mL for telmisartan 40 mg, 693 +/- 606 ng/mL for telmisartan 80 mg, and 1635 +/- 1406 ng/mL for telmisartan 120 mg. Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40, 80, and 120 mg are at the plateau region of the concentration-response curve. All active treatments were well tolerated, with tolerability profiles similar to placebo, and telmisartan did not produce any clinically relevant first-dose effects. These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan.

The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Intravenous Dipyridamole Thallium Imaging Study Group.

Clinical data on 3,911 patients were collected from 64 individual investigators to evaluate the safety of intravenous dipyridamole-thallium imaging as an alternative to exercise thallium imaging for the evaluation of coronary artery disease. There were two deaths because of myocardial infarctions, two nonfatal myocardial infarctions, and six cases of acute bronchospasm. Chest pain occurred in 770 patients (19.7%). Headache and dizziness were reported by 476 patients (12.2%) and 460 patients (11.8%), respectively. ST-T changes on the electrocardiogram were seen in 292 patients (7.5%). Use of parenteral aminophylline to treat adverse events associated with intravenous dipyridamole brought complete relief of symptoms in 439 of 454 patients (96.7%). There is a potential for increased risk for serious ischemic events in patients with a history of unstable angina who are administered intravenous dipyridamole. In patients with acutely unstable angina (i.e., continuing chest pain) or in the acute phase of myocardial infarction, use of intravenous dipyridamole in thallium scintigraphy should be avoided. There is also an increased risk for bronchospasm in patients with a history of asthma; acute bronchospasm can be relieved immediately by administration of aminophylline. These results demonstrate that intravenous dipyridamole-thallium scintigraphy is a relatively safe, noninvasive technique for the evaluation of coronary artery disease.

Personality and risk of cancer: 20-year follow-up of the Western Electric Study.

Psychologic depression as measured by the Minnesota Multiphasic Personality Inventory (MMPI) in a cohort of 2018 middle-aged men employed at the Western Electric Company in 1957-1958 was positively associated with 20-year incidence and mortality from cancer. The association with incidence was apparent only during the first 10 years of follow-up, but the association with mortality was observed for the full 20 years of follow-up. The association persisted after adjustment for age, number of cigarettes smoked, alcohol intake, occupational status, family history of cancer, body mass index, and serum cholesterol. The association did not appear to be stronger for one type of cancer than another, but the power of this study to detect differences among types of cancer was limited by small numbers. However, the association did appear to be stronger with risk of fatal cancer than with total incidence. No association was noted between other variables measured by the MMPI or Cattell 16 Personality Factor Inventory and subsequent incidence or mortality from cancer. Specifically, the data did not support the hypothesis that psychologic repression, as measured by Welsh R scale in the MMPI, would be associated with risk of cancer. These results are consistent with previously reported results that have suggested that psychologic depression might promote the development and spread of malignant neoplasms.