Assessment of optimal insulin administration timing for standard carbohydrates-rich meals using continuous glucose monitoring in children with type 1 diabetes: A cross-over randomized study.

AIMS/INTRODUCTION: The present study was an assessment of postprandial glucose concentration after carbohydrates-rich meals using continuous glucose monitoring in 30 children with type 1 diabetes treated using continuous subcutaneous insulin infusion with a rapid-acting insulin analog. MATERIALS AND METHODS: Over a period of 3 days, participants administered simple boluses with different delay times between insulin administration and the beginning of carbohydrates-rich meal consumption (meal no. 1 containing 197 kcal, no. 2 containing 247 kcal and meal no. 3 containing 323 kcal; containing practically no protein and fat). In the present cross-over randomized study, we analyzed the average glucose concentration profiles in 5-min intervals, mean glucose at insulin administration, mean glucose after 120 and 180 min, mean and peak glucose, glucose peak time, areas under the glucose and glucose increase curves, and time period lengths with glucose <50, 70 mg/dL, and >140 and 200 mg/dL. RESULTS: For test meals at 20-min versus 0-min delay time, the study exposed a longer median time period to reach peak glucose (95 vs 65 min, P = 0.01) after meals. A tendency to the lowest peak and mean glucose, and the longest time with glucose within a normal range was observed in patients who administered bolus insulin 20 min before a meal. CONCLUSIONS: For carbohydrates-rich meals, administration of a proper dose of a rapid-acting insulin analog is crucial. The influence of rapid-acting insulin analog administration timing seems to be of minor importance in comparison with correct insulin dose adjustment; however, a tendency to achieve more balanced glucose profiles was found in a group who administered insulin 20 min before a meal.

Pharmaceutical quality evaluation of different glimepiride brands marketed in Karachi (Pakistan): In pursuance to global issue of availability and affordability of quality medicines.

Availability of economical quality medicines is always required for chronic disease management. Price differences among multiple brands of a product do not essentially displays low quality for the more affordable brand, however in a few occurrences it appears. Glimepiride, an oral anti-diabetic drug, is produced by several national and multinational industries in Pakistan with considerable cost variation. The study aimed to evaluate the quality and economy of various Glimepiride brands available in Karachi, specifically of public sector hospitals. For this, eight glimepiride brands were collected and analyzed for the pharmaceutical quality using physical parameters, disintegration test, dissolution profile, spectrophotometric assay and content uniformity. Pharmacoeconomic assessment was also carried out such as availability, affordability and price variation. A profound discrepancy was observed among the prices of selected brands. All of the products found to be equivalent to the reference product except G5, the most inexpensive and highest consumed product of a public sector hospital. Study concludes that products with higher quality and lesser price can be used as a substitute to the costly brands while availability of a substandard product looks for consideration of pertinent authorities to assure the distribution of quality medicines.

Variability in Potency Among Commercial Preparations of Berberine.

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

The consumer welfare implications of governmental policies and firm strategy in markets for medicines.

This paper empirically examines the consumer welfare implications of changes in government policies related to patent protection and compulsory licensing in the Indian market for oral anti-diabetic (OAD) medicines. In contrast to previous studies on the impact of pharmaceutical patents in India, we observe, and estimate the welfare effects accruing from differential pricing and voluntary licensing strategies of patent-holding innovator firms. Three novel molecules belonging to the dipeptidyl peptidase-4 (DPP-4) inhibitor class of OADs have been launched in India by the patent holders, at lower prices than those prevailing in the developed countries. Using aggregate market transaction data, we structurally estimate demand and supply and use the parameter estimates in our model to simulate consumer welfare under various counterfactual scenarios. Our results suggest that the introduction of DPP-4 inhibitors generated a consumer surplus gain of around 7.6 cents per day for a typical DPP-4 inhibitor user under the existing differential pricing and voluntary licensing strategies. If the innovators decide to price at developed-country levels, this surplus is eliminated almost entirely. The issuance of compulsory licensing does not always improve consumer welfare because if innovators defer or delay the introduction of new drugs in response, the loss in consumer welfare could be substantial.

Biosimilar insulins.

Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.

[Economic evaluation of drugs. Effectiveness in diabetes therapy]. / Okonomische Bewertung von Arzneimitteln. Effizienz in der Diabetestherapie.

The article explains the systematic manner of applying important basic principles to economic aspects within the health system and also makes transparent the basic principles of cost minimization. In health economics the concern is not cost minimization but optimization of the relationship between cost and medical effectiveness. It is important to realize that health economic evaluation has to take into account not only pure acquisition costs of a drug but also the costs connected with its being prescribed.

Safety of nateglinide as used in general practice in England: results of a prescription-event monitoring study.

Nateglinide (Starlix((R))) is licensed for the treatment of Type 2 diabetes in patients inadequately controlled with metformin. The study objective was to monitor the safety and use of nateglinide prescribed by primary care physicians (GPs) in England, using the observational cohort technique, Prescription-Event Monitoring. Exposure data were derived from dispensed nateglinide prescriptions issued October 2001-June 2004; demographic and outcome data, from questionnaires sent to patients' GPs at least 6 months after patients' first prescription. Incidence densities (IDs; number of first reports of an event/1,000 patient-months exposure) were calculated for month 1 (ID(1)), months 2-6 (ID(2-6)); rate differences [ID(1)-ID(2-6) (+99% CI)] were examined. Cohort comprised 4,557 patients, median age 60 (IQR 51, 68 years); 2,439 (53.5%) male; 3,463 (76.0%) received nateglinide in combination with metformin. GPs reported 1,625 reasons for stopping in 1,474 (32.3%) patients and 80 events as adverse drug reactions in 66 (1.5%) patients. Events associated with starting treatment included nausea/vomiting [ID(1)-ID(2-6) 9.6 (99% CI 5.3, 13.9)], malaise/lassitude [ID(1)-ID(2-6) 6.03 (99% CI 2.2, 9.9)]. No serious hypersensitivity reactions were reported. Two pregnancies (< 0.1%) and 73 deaths (1.6%) were reported. Nateglinide appeared to be generally well tolerated when used in combination with metformin for the treatment of Type 2 diabetes.

Making the unit of insulin: standards, clinical work, and industry, 1920-1925.

The standardization of insulin is generally considered by historians to have been a process conducted by physiologists under the direction of Henry Dale. This article shows that it actually involved many actors and began with the earliest administration to patients in Canada and the United States. During this first phase, the drug company Eli Lilly also contributed actively to the standardization, under the scientific direction of George Clowes. This is not to undermine the role of Dale, whose political leadership was paramount for the international phase of the standardization. His scientific contribution, however, was a continuation of previous work led by physiologists, clinicians, and pharmacists. The production and packaging of insulin in standardized units thus appears to be the result of the impressive working of a transdisciplinary and transnational network. It also highlights how new modes of drug regulation were elaborated by state bodies in the early 1920s and paved the way for more extensive reforms.