Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial.

AIM: to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy. METHODS: patients with type 2 diabetes and an HbA(1c) of 6.5-9.0% while on a stable dose of metformin (≥ 1500 mg/day) combined with diet and exercise for at least 12 weeks were randomized in a double-blind manner to receive either sitagliptin 100 mg daily (N = 516) or glimepiride (starting dose 1 mg/day and up-titrated, based upon patient's self-monitoring of blood glucose results, to a maximum dose of up to 6 mg/day) (N = 519) for 30 weeks. The primary analysis assessed whether sitagliptin is non-inferior to glimepiride in reducing HbA(1c) at week 30 (based on the criterion of having an upper bound of the 95% CI less than the prespecified non-inferiority bound of 0.4%). RESULTS: the mean baseline HbA(1c) was 7.5% in both the sitagliptin group (n = 443) and the glimepiride group (n = 436). After 30 weeks, the least squares (LS) mean change in HbA(1c) from baseline was -0.47% with sitagliptin and -0.54% with glimepiride, with a between-group difference (95% CI) of 0.07% (-0.03, 0.16). This result met the prespecified criterion for declaring non-inferiority. The percentages of patients with an HbA(1c) < 7.0% at week 30 were 52 and 60% in the sitagliptin and glimepiride groups, respectively. The LS mean change in fasting plasma glucose from baseline (95% CI) was -0.8 mmol/l (-1.0, -0.6) with sitagliptin and -1.0 mmol/l (-1.2, -0.8) with glimepiride, for a between-group difference (95% CI) of 0.2 mmol/l (-0.1, 0.4). The percentages of patients for whom hypoglycaemia was reported were 7% in the sitagliptin group and 22% in the glimepiride group (percentage-point difference = -15, p < 0.001). Relative to baseline, sitagliptin was associated with a mean weight loss (-0.8 kg), whereas glimepiride was associated with a mean weight gain (1.2 kg), yielding a between-group difference of -2.0 kg (p < 0.001). CONCLUSIONS: in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy, the addition of sitagliptin or glimepiride led to similar improvement in glycaemic control after 30 weeks. Sitagliptin was generally well tolerated. Compared to treatment with glimepiride, treatment with sitagliptin was associated with a lower risk of hypoglycaemia and with weight loss versus weight gain (ClinicalTrials.gov: NCT00701090).

[Caspofungin after solid organ transplantation in Germany: observational study on treatment of invasive fungal infections]. / Caspofungin nach Transplantation solider Organe in Deutschland: Beobachtungsstudie zur Behandlung invasiver Pilzinfektion.

BACKGROUND: This study was a pre-planned country-specific secondary analysis of results in Germany from a multinational multicenter observational study to retrospectively evaluate clinical outcomes with caspofungin in patients with probable and proven invasive fungal infection following solid organ transplantation (SOT). METHODS: Data were retrospectively collected on a single episode of invasive fungal infection (IFI) in patients who had a SOT between January 2004 and June 2007. Effectiveness was reported as the proportion of patients who received at least five doses of caspofungin with a favorable (complete or partial) response. Safety was assessed for patients who received at least one dose of caspofungin. Descriptive statistics were employed for all evaluations. RESULTS: A total of 41 SOT patients (27 male, 14 female; median age 56 years, median APACHE II score at start of caspofungin therapy 23) were enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and liver (46%). Prevalent risk factors for IFI at baseline were use of central venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients, 90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of SOT procedure >5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in 34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy for IFI, in most cases because they were refractory to prior antifungal drugs. Immunosuppressants were administered with caspofungin in 39 out of 41 patients (95%). In subjects with at least 5 doses of caspofungin (modified intention to treat population) the favorable response rate at the end of caspofungin therapy was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%), 86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with combination therapy. No (serious) adverse events or drug interactions related to treatment with caspofungin were reported. The overall survival rate was 79% (26 out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin treatment. CONCLUSION: Caspofungin was found to be an effective treatment of probable and proven invasive fungal infections in patients following SOT in Germany.

Company reference estimates for productivity loss due to migraine and productivity gains using rizatriptan 10 mg in Germany.

The prevalence of migraine in Germany is up to 14% in the female and up to 8% in the male population and peaks between the age of 35 and 45. Few studies have investigated the productivity loss and resulting costs attributable to migraine in Germany or addressed the question whether these costs can be reduced by optimal treatment. In recent years, 5-HT(1B/D) agonists (so-called triptans), a generation of drugs highly specific for migraine treatment, have been introduced. Seven 5-HT(1B/D) agonists have been approved in Germany with more than 20 dosage forms. We present a model that enables employers to estimate the annual cost of migraine and the annual cost that could be saved by treatment of migraine with rizatriptan compared with the use of non-specific antimigraine medication. A representative German company with 10,000 employees is used for the reference case analysis. This company is predicted to have 580 female and 284 male employees with migraine. These employees are estimated to lose 6992 workdays or 31.8 person years of productive effort annually due to migraine, valued approximately 1,431,719 euros. The value of work loss that could be avoided by treating migraine with rizatriptan is estimated at 619,094 euros annually. These data indicate that costs arising from lost productivity can be reduced by treating migraine headaches with a triptan.

Migraine consultation patterns in primary care. Results from the PCAOM study 1994-96.

In order to establish a basis for the planning of improved medical care of migraine in Germany, we report on the proportion of migraine patients under primary care and the continuity of consultations for migraine as determined by age, gender, and history of migraine and nonmigraine practice contact (Primary Care of Migraine, PCAOM Study). A primary-care-physician-based migraineurs' sample of 16,573 women and 4,636 men (MediPlus, IMS Health) was placed in relation to cases expected according to International Headache Society criteria in the base population, and was followed for up to 3 years for repeat consultations. Overall, no more than 51% and 37%, respectively, of female and male statutory health-insured migraine headache sufferers had a migraine diagnosis mentioned at least once a year in primary care. At younger ages, substantially less advantage was taken of available primary healthcare for migraine; 79% of the women and 74% of the men were estimated to present again to the same primary-care physician within 3 years because of migraine, the corresponding figures for patients with no history of migraine in the practice concerned being 41% and 31%, respectively. Following first migraine contacts, time to recontact and quarterly recontact prevalences for migraine did not differ, whether on the basis of an established nonmigraine primary care relationship or a first encounter with a medical practice. Trust evidenced by an existing nonmigraine doctor-patient relationship apparently did not carry over to migraine. Results indicate that one of the greatest challenges in relation to the care of migraine patients in Germany is to establish and maintain solid doctor-patient relationships.

Simvastatin after orthotopic heart transplantation. Costs and consequences.

OBJECTIVE: Recent data indicate that the combination of a low cholesterol diet and simvastatin following heart transplantation is associated with significant reduction of serum cholesterol levels, lower incidence of graft vessel disease (GVD) and significantly superior 4-year survival rates than dietary treatment alone. On the basis of this first randomised long term study evaluating survival as the clinical end-point, we investigated the cost effectiveness of the above regimens as well as the long term consequences for the patient and for heart transplantation as a high-tech procedure. DESIGN AND SETTING: The perspective of the economic analysis was that of the German health insurance fund. Life-years gained were calculated on the basis of the Kaplan-Meier survival curves from the 4-year clinical trial and from the International Society for Heart and Lung Transplantation (ISHLT) overall survival statistics. Incremental costs and incremental cost-effectiveness ratios were determined using various sources of data, and both costs and consequences were discounted by 3% per year. Sensitivity analyses using alternative assumptions were conducted in addition to the base-case analysis. PATIENTS AND PARTICIPANTS: As in the original clinical trial, the target population of the economic evaluation comprised all heart transplant recipients on standard triple immunosuppression consisting of cyclosporin, azathioprine and prednisolone, regardless of the postoperative serum lipid profile. INTERVENTIONS: The therapeutic regimens investigated in the analysis were the American Heart Association (AHA) step II diet plus simvastatin (titrated to a maximum dosage of 20 mg/day) and AHA step II diet alone. MAIN OUTCOME MEASURES AND RESULTS: Four years of treatment with simvastatin (mean dosage 8.11 mg/day) translated into an undiscounted survival benefit per patient of 2.27 life-years; 0.64 life-years within the trial period and 1.63 life-years thereafter. Discounted costs per year of life gained were $US1050 (sensitivity analyses $US800 to $US15,400) for simvastatin plus diet versus diet alone and $US18,010 (sensitivity analyses $US17,130 to $US21,090) for heart transplantation plus simvastatin versus no transplantation (all costs reflect 1997 values; $US1 = 1.747 Deutschmarks). CONCLUSIONS: Prevention of GVD with simvastatin after heart transplantation was cost effective in all the scenarios examined with impressive prolongation of life expectancy for the heart recipient. Simvastatin also achieved an internationally robust 21% improvement in the cost effectiveness of heart transplantation compared with historical cost-effectiveness data.

Migraine prescription density and recommendations. Results of the PCAOM Study.

We estimate the extent to which recommendations on the prevention and treatment of migraine issued by professional medical bodies are implemented in medical practice in Germany. Computerized data (MediPlus, IMS Health) were analyzed in 4,636 male and 16,573 female migraineurs from 383 primary care practices 1994 through 1996 (Primary Care of Migraine, PCAOM study). A total of 90,540 drug prescriptions with a documented diagnosis of migraine were issued in 45,669 person-years (1,492 prescriptions [DM 40.99] per person-year to men, 2,109 prescriptions [DM 62.01] per person-year to women). Approximately three of every four prescriptions were incompatible with the recommendations of the German Migraine and Headache Society (DMKG), amounting to extrapolated costs of DM 49 million per year borne by the German statutory health insurance fund for combination migraine preparations. The density of non-DMKG therapies for diagnosed migraine followed a sigmoid curve with increasing patient age, while DMKG-compliant therapies described a bell-shaped curve. Referrals to neurological care specialists were not associated with subsequent primary care focus on recommended therapies. We conclude that medication prescribed for migraine is largely not according to long-standing recommendations by medical societies in Germany.

Outpatient costs of osteoporosis in a national health insurance population.

There are few valid data on the outpatient diagnosis and treatment of osteoporosis in Germany, despite the high prevalence of this disease and the high costs associated with its complications. We therefore conducted a retrospective cohort study to investigate the prevalence of documented osteoporosis and the use of health care resources in its outpatient treatment in a representative random sample of 7490 patients from the Dresden area who were insured under the national health insurance program for a 1-year period from the 3rd quarter of 1993 to the 2nd quarter of 1994. Documented cases of osteoporosis were identified by International Statistical Classification of Diseases, 10th Revision diagnostic codes M80 to M82, and the costs of diagnostic services for osteoporosis were calculated using a uniform fee schedule. Specific and nonspecific osteoporosis medications were classified using a published anatomic-therapeutic-chemical code, and their costs were calculated on the basis of pharmacy sales prices. Three age- and sex-matched controls without documented osteoporosis (n = 705) were assigned for each case patient in estimating the net use of resources. Data for the region, as well as age-standardized information for the overall German national health insurance system, were calculated. The 1-year prevalence of documented osteoporosis in the region was 3.14% (5.20% in women, 0.89% in men), and the age-standardized prevalence in the German national health insurance system was 2.25%. During the study period, 51.1% of the cases and 2.1% of the controls were examined by osteodensitometry. Patients received 106 defined daily doses of osteoporosis medications during the year; 37.0% of the prescribed daily doses were for sodium fluorophosphate/calcium combinations, 4.3% were for sodium fluoride, and 7.7% were for calcium alone. Sex hormones and calcitonin each accounted for 7.7% of the prescribed daily doses. Only a fraction of epidemiologically expected cases of osteoporosis have been identified and documented in the outpatient sector. Only approximately 50% of these receive osteoporosis-specific therapy, and compliance with therapy is low. To reduce osteoporosis-associated fracture rates, which are extremely cost intensive and greatly impair patients' quality of life, more consistent treatment is needed.