Elizabeth Round

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes.

BackgroundIn a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies.MethodsThe present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events.ResultsSummary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events.ConclusionsIn this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.

Finasteride in the treatment of men with frontal male pattern hair loss

BACKGROUND Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis

BackgroundSitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, is the first in a new class of oral antihyperglycemic agents (AHAs) for the treatment of patients with type 2 diabetes. Type 2 diabetes is a life-long disease requiring chronic treatment and management. Therefore, robust assessment of the long-term safety and tolerability of newer therapeutic agents is of importance. The purpose of this analysis was to assess the safety and tolerability of sitagliptin by pooling 12 large, double-blind, Phase IIb and III studies up to 2 years in duration. Methods: This analysis included 6139 patients with type 2 diabetes receiving either sitagliptin 100 mg/day (N = 3415) or a comparator agent (placebo or an active comparator) (N = 2724; non-exposed group). The 12 studies from which this pooled population was drawn represent the double-blind, randomized, Phase IIB and III studies that included patients treated with the clinical dose of sitagliptin (100 mg/day) for at least 18 weeks up to 2 years and that were available in a single safety database as of November 2007. These 12 studies assessed sitagliptin as monotherapy, initial combination therapy with metformin, or add-on combination therapy with other oral AHAs (metformin, pioglitazone, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone). Patients in the non-exposed group were taking placebo, pioglitazone, metformin, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone. This safety analysis used patient-level data from each study to evaluate clinical and laboratory adverse experiences.ResultsFor clinical adverse experiences, the incidence rates of adverse experiences overall, serious adverse experiences, and discontinuations due to adverse experiences were similar in the sitagliptin and non-exposed groups. The incidence rates of specific adverse experiences were also generally similar in the two groups, with the exception of an increased incidence rate of hypoglycemia observed in the non-exposed group. The incidence rates of drug-related adverse experiences overall and discontinuations due to drug-related adverse experiences were higher in the non-exposed group, primarily due to the increased incidence rate of hypoglycemia in this group. For cardiac- and ischemia-related adverse experiences (including serious events), there were no meaningful between-group differences. No meaningful differences between groups in laboratory adverse experiences, either summary measures or specific adverse experiences, were observed.ConclusionIn patients with type 2 diabetes, sitagliptin 100 mg/day was well tolerated in clinical trials up to 2 years in duration.

Global photographic assessment of men aged 18 to 60 years with male pattern hair loss receiving finasteride 1 mg or placebo

BACKGROUND Finasteride (1 mg) has been shown to increase vertex hair growth in men aged 18 to 60 years with male pattern hair loss and to increase frontal scalp hair growth in subjects aged 18 to 41 years. OBJECTIVE A secondary efficacy analysis was conducted to determine effects of finasteride (1 mg) on scalp hair growth in the 4 distinct scalp regions affected by male pattern hair loss. METHODS Multicenter, double-blind studies randomized patients with vertex hair loss (men aged 18-41 and 41-60 years) to finasteride (1 mg/d) or placebo. Efficacy was evaluated by review of standardized clinical photographs (global photographic assessment) of the vertex, anterior/mid scalp regions, and frontal and temporal hairlines over 24 months relative to baseline. RESULTS At 24 months, treatment with finasteride resulted in statistically significant (P ≤ .05) hair growth versus placebo in all scalp regions. There was also a significant decrease in hair loss in the younger men treated with finasteride in all areas, but only in the vertex and anterior/mid scalp regions in the older men. A slightly higher incidence of drug-related sexual adverse experiences was reported in the finasteride group than in the placebo group, irrespective of age. LIMITATIONS These studies enrolled men with vertex pattern hair loss; therefore, the findings may not be extrapolated to men with predominantly anterior/mid scalp, frontal, or temporal hair loss. CONCLUSION Based on global photographic assessment, finasteride (1 mg) is able to increase hair growth in all areas of the scalp affected by male pattern hair loss.

Clinical Experience of the Detection of Prostate Cancer in Patients with Benign Prostatic Hyperplasia Treated with Finasteride

AbstractThe clinical experience relating to the detection of prostate cancer in patients participating in 2 large multicenter clinical trials of finasteride in the treatment of benign prostatic hyperplasia is reviewed. A total of 1,645 patients 40 to 83 years old with benign prostatic hyperplasia was randomized to receive 1 or 5mg. finasteride or placebo once a day for 12 months in a double-blind fashion followed by an open extension study in which all patients were treated with 5mg. finasteride daily. At entry, all patients were to have a maximum urinary flow rate of 15ml. per second or less with a voided volume of 150ml. or more, an enlarged prostate and symptoms of urinary obstruction. Patients with a prostate specific antigen level of 40ng./ml. or more, or any finding suggestive of prostate cancer were excluded. During the study period 32 cases of prostate cancer were diagnosed: 12 were detected during the 12 months of the controlled study and were evenly distributed among the treatment groups (4 on p...

Progression of hair loss in men with androgenetic alopecia (male pattern hair loss): long-term (5-year) controlled observational data in placebo-treated patients

Relatively little is known about the progression of androgenetic alopecia (AGA; male pattern hair loss) in untreated men. We evaluated the long-term (5-year) progression of AGA in men treated with placebo in a controlled clinical trial setting. We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA. Each study consisted of an initial 1-year, randomized, double-blind, placebo-controlled base study and four consecutive, 1-year, double-blind, placebo-controlled extension studies. Change over time in scalp hair growth was evaluated by four predefined endpoints: scalp hair counts; assessment of standardized clinical photographs by an expert panel; investigator clinical assessment; and patient self-assessment. All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period, with a loss of 239 hairs from baseline (26.3% decline in hair density) measured in the target area at 5 years (p < 0.001 vs. baseline). Similarly, visible progression of scalp hair loss was demonstrated by global photographic assessment, with 75% of placebo patients rated as worsened from baseline at 5 years. We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA.

A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control

Type 2 diabetes mellitus (T2DM) treatment generally requires multiple antihyperglycemic agents. When diet, exercise, and treatment with sulfonylurea and metformin do not achieve glycemic goals, several options are available. The present study evaluated the efficacy and tolerability of sitagliptin 100 mg/day added to therapy with sulfonylurea and metformin.

Erratum to: Safety and Tolerability of Sitagliptin in Type 2 Diabetes: Pooled Analysis of 25 Clinical Studies.

The author of the above-mentioned paper would like to make the following adjustments to their article. In the Results section, under ‘Predefined Laboratory Abnormality Criteria’ and the subsection ‘Liver Enzymes’, the sentence in the first paragraph ‘‘...the proportion of patients whose last ALT measurement was C3 times the ULN were 0.8% and 0.6%, respectively [between-group difference 0.0]....’’, should state the ALT between-group difference as 0.2, rather than 0.0. In Table 3, the difference between Sitagliptin and Non-exposed (95% CI) for Neoplasms Benign, Malignant and Unspecified should read 0.5 (0.0, 1.0), rather than 0.6 (-0.0, 1.2). In Table 5, the lower bound for Dyspepsia should read 0.1, rather than 0.0. In Table 6 of the Appendix, the number of patients (N) is stated incorrectly in the second and third sections of the table. The N values in all sections should read: Sitagliptin group (N = 7,726) and Non-exposed group (N = 6,885). In Table 7 of the Appendix, the lower bound for Dyspepsia should read 0.1, not 0.0. Also, footnote ‘c’ should include ‘‘gastrointestinal pain’’. The authors thank Springer Healthcare for publishing the corrections.