A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. RESULTS: There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). CONCLUSIONS: A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

A prospective evaluation of cimetidine drug use.

A drug utilization evaluation (DUE) of cimetidine surveyed use, dose, route of administration, indications, and safety in five New York hospitals. Drug use and patient information were recorded on cimetidine data collection forms; data on indications were noted on physician response forms. In addition to FDA-approved indications, cimetidine was frequently used for non-approved indications substantiated by the H2-antagonist literature. Prophylaxis accounted for 42.5% of total use, followed by nonulcer (25.5%), ulcer (18.8%), and other indications (13.1%). Appropriateness of dosage could not be determined in 42 (16.1%) patients with insufficient creatinine clearance data. One hundred and thirty patients (49.8%) whose renal function could be estimated were within dosage guidelines; 89 (34.1%) were above or below dosage recommendations. The incidence of adverse effects was low (3.83%), although many patients were "at risk" of untoward events or drug-drug interactions.

Macro-monitoring: a step toward rational psychopharmacotherapy.

A 15-item checklist was used to monitor the drug therapy of 516 patients in five clinical settings. The primary purpose of this study was to determine the extent of irrational drug use in these several settings. After gathering baseline data, two similar clinical units were selected for a six-month follow-up to determine the impact of drug consultation by an expert clinical psychopharmacologist. In the unit where drug consultation was provided, there was a significnat reduction in extended antiparkinsonian agent use (p less than 0.001), multiple daily dosage (p less than 0.001), inappropriate anxiolytic use (p less than 0.01), polypharmacy (p less than 0.001) and too rapid change in medication (p less than 0.01). The unit that did not have drug consultation continued to have a high percentage of patients receiving drugs in an inappropriate manner. Although the consultant had a significant impact on drug use, it was recognized that such consultation is not feasible for most psychiatric facilities. The checklist itself is a systematic tool that can be used to identify prescribing practices of questionable appropriateness. If used properly by the pharmacist, the checklist can serve as a supportive system to assist the physician in providing better patient care.