Importance of early insulin secretion. Comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes

WSTĘP. Badanie przeprowadzono w celu porównania wpływu nateglinidu, gliburydu i placebo na poposiłkowe zwyżki glikemii oraz wydzielanie insuliny u chorych na cukrzycę typu 2 leczonych uprzednio dietą. MATERIAŁ I METODY. Badanie przeprowadzono metodą podwójnie ślepej próby, z udziałem grupy kontrolnej. Randomizacją objęto 152 chorych z kilku ośrodków. Otrzymywali oni przez 8 tygodni nateglinid (120 mg przed posiłkiem 3 razy dziennie, n = 51) lub gliburyd (5 mg 4 razy dziennie, po 2 tygodniach dawkę zwiększano do 10 mg 4 razy dziennie, n = 50) lub placebo (n = 51). Tydzień przed rozpoczęciem badania oraz po 8 tygodniach leczenia wykonywano oznaczenie profilu glikemii, insulinemii oraz stężenia peptydu C po prowokacji w postaci pokarmów płynnych. Tydzień przed badaniem oraz po 7 tygodniach terapii na podstawie 19 pomiarów określano dzienny profil glikemii i insulinemii. Chorzy spożywali w ciągu tego okresu 3 posiłki stałe. WYNIKI. Po spożyciu pokarmów płynnych nateglinid skuteczniej zmniejszał przyrostowe pole pod krzywą (AUC, area under the curve) dla glukozy niż gliburyd (D = -4,94 vs. -2,71 mmol &#8226; h/l, p < 0,05), zaś gliburyd skuteczniej niż nateglinid obniżał stężenie glukozy w osoczu na czczo (D = -2,9 vs. -1,0 mmol/l, p < 0,001). Natomiast wzrost stężenia peptydu C wywołany przez gliburyd był większy niż w przypadku nateglinidu (D = +1,83 vs. +0,95 nmol &#8226; h/p < 0,01) i jedynie gliburyd zwiększał stężenie insuliny na czczo. Po prowokacji w formie pokarmów stałych zarówno nateglinid, jak i gliburyd zapewniały podobną całkowitą kontrolę glikemii (D 12-h AUC przyrostowe = -13,2 vs. -15,3 mmol &#8226; h/l), lecz AUC dla insuliny w przypadku nateglinidu było wyraźnie mniejsze niż w przypadku gliburydu (D 12-h AUC = +866 vs. +1702 pmol &#8226; h/l, p = 0,01). WNIOSKI. Badanie to wykazało, że nateglinid wybiórczo zwiększał wczesne wydzielanie insuliny i zapewniał lepszą kontrolę glikemii w czasie spożywania posiłków niż gliburyd, powodując jednocześnie mniejszą całkowitą ekspozycję na insulinę niż gliburyd.INTRODUCTION. This study compared the effects of nateglinide, glyburide, and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS. This randomized, double-blind, placebo-controlled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n = 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51) for 8 weeks. Glucose, insulin, and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8. At weeks &#8212; 1 and 7, 19-point daytime glucose and insulin profiles, comprising three solid meals, were measured. RESULTS. During the liquid-meal challenge, nateglinide reduced the incremental glucose area under the curve (AUC) more effectively than glyburide (D = &#8211;4.94 vs. &#8211;2.71 mmol &#8226; h/l, p < 0.05), whereas glyburide reduced fasting plasma glucose more effectively than nateglinide (D = &#8211;2.9 vs. &#8211;1.0 mmol/l, respectively, p < 0.001). In contrast, C-peptide induced by glyburide was greater than that induced by nateglinide (D = +1.83 vs. +0.95 nmol &#8226; h/l, p < 0.01), and only glyburide increased fasting insulin levels. During the solid meal challenges, nateglinide and glyburide elicited similar overall glucose control (D 12-h incremental AUC = &#8211;13.2 vs. &#8211;15.3 mmol &#8226; h/l), but the insulin AUCinduced by nateglinide was significantly less than that induced by glyburide (D 12-h AUC = +866 vs. +1,702 pmol &#8226; h/l, p = 0.01). CONCLUSIONS. This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide

Effect of vildagliptin as add-on therapy to a low-dose metformin

AIM: To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus (T2DM) patients who have inadequate control with metformin monotherapy

Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus

To compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes. This 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite > or =3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels < or =7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia. At end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/dL; 95% confidence interval, -47.6 to -22.2; P<.0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatment-emergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose <70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P<.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups. The addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in <5% of patients in the insulin glargine treatment group

Multiple-dose pharmacokinetics of peginterferon alfa-2b in patients with renal insufficiency

What is already known about this subject?Current therapy for hepatitis C typically consists of pegylated interferon (PEG-IFN) alfa in combination with ribavirin.Pegylation of IFN alfa-2b confers a 10-fold increase in elimination half-life and a 30% reduction in volume of distribution compared with non-PEG-IFN alfa-2b.A single-dose pharmacokinetic study conducted in patients with chronic renal dysfunction has shown that renal elimination accounts for 30% of total PEG-IFN alfa-2b clearance and that PEG-IFN alfa-2b exposure increases with severity of renal insufficiency.What this study addsBecause the primary mechanism of IFN clearance is catabolism in the kidney, appropriate dosing of IFN-based therapies in patients with renal insufficiency is an important issue.This multiple-dose pharmacokinetic study shows that exposure to PEG-IFN alfa-2b is increased in patients with renal insufficiency, suggesting that doses of the drug should be reduced by 50% in patients with severe renal insufficiency and by 25% in those with moderate insufficiency.PEG-IFN alfa-2b was well tolerated in all patient groups during the 4-week treatment period, with similar adverse events occurring in patients with renal insufficiency and in those with normal renal function