Greater Reductions In Fasting Plasma Glucose Research Articles

Switching to iGlarLixi versus continuation of a daily or weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) in insufficiently controlled type 2 diabetes: A LixiLan-G trial subgroup analysis by HbA1c and GLP-1 RA use at screening.

AimIn people with type 2 diabetes (T2D) requiring intensification beyond glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and oral antihyperglycaemic drugs (OADs), switching to iGlarLixi was shown to be efficacious and well‐tolerated in the LixiLan‐G trial. This exploratory analysis of LixiLan‐G assessed the efficacy and safety of switching to iGlarLixi versus continuing GLP‐1 RA therapy, stratified by screening HbA1c level (≥7.0 to ≤7.5 %; >7.5 to ≤8.0 %; >8.0 to ≤9.0 % [≥53 to ≤58 mmol/mol; >58 to ≤64 mmol/mol; >64 to ≤75 mmol/mol]) and previous GLP‐1 RA regimen at screening (once/twice daily or once weekly).Materials and MethodsEndpoints for all subgroups included: change in HbA1c, achievement of HbA1c <7 % and hypoglycaemia events. Adverse events and changes in fasting plasma glucose (FPG), 2‐hour postprandial plasma glucose (PPG), 2‐hour PPG excursion and weight were analysed according to previous GLP‐1 RA regimen.ResultsSwitching to iGlarLixi in all subgroups resulted in significantly greater reductions in HbA1c and proportions of participants reaching HbA1c <7 % (including with no documented hypoglycaemia) at Week 26 compared with continued GLP‐1 RA treatment. Switching to iGlarLixi also led to significantly greater reductions in FPG, 2‐hour PPG, and 2‐hour PPG excursion, irrespective of previous GLP‐1 RA regimen. Rates of hypoglycaemia were low, but slightly higher in those who switched to iGlarLixi for all subgroups. Modest weight gain was seen with iGlarLixi, irrespective of previous GLP‐1 RA regimen.ConclusionsSwitching to iGlarLixi improved glycaemic control, regardless of screening HbA1c or previous GLP‐1 RA type, offering a simple, efficacious and well‐tolerated treatment intensification option for people with T2D inadequately controlled by GLP‐1 RAs and OADs.

Clinical perspectives from the BEGIN and EDITION programmes: Trial-level meta-analyses outcomes with either degludec or glargine 300 U/mL vs glargine 100 U/mL in T2DM

AimsTo explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes. MethodsMeta-analyses of HbA1c, fasting plasma glucose (FPG), average 24h self-measured plasma glucose (SMPG), pre-breakfast SMPG and hypoglycaemia incidence and rate, using data from the BEGIN (IDeg) and EDITION (Gla-300) insulin development programmes, were performed. ResultsIn BEGIN, despite greater FPG reduction with IDeg than Gla-100, HbA1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA1c change: 0.09 [0.01–0.18] %) whereas in EDITION, there was no difference in FPG and HbA1c reduction between Gla-300 and Gla-100. Risk of nocturnal confirmed (<3.1mmol/L [<56mg/dL]) or severe hypoglycaemia, but not anytime (24h) events, was lower with IDeg than Gla-100 (relative risk [RR] 0.79 [0.66–0.94]) whereas Gla-300 was associated with reduced risk of nocturnal (RR 0.75 [0.61–0.92]) and anytime (24h) (RR 0.81 [0.69–0.94]) confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia versus Gla-100. ConclusionsThese trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA1c reduction to Gla-100, accompanied by lower risk of hypoglycaemia both at night and at any time of day. Gla-300 and IDeg appear more similar than dissimilar, but head-to-head trials are required.

Association of KCNQ1 polymorphisms with gliclazide efficacy in Chinese type 2 diabetic patients.

To investigate the effects of KCNQ1 polymorphisms on the efficacy of gliclazide in type 2 diabetic patients. A total of 443 newly diagnosed type 2 diabetic patients were included in this study. After enrollment, patients went on an 8-week gliclazide monotherapy. Fasting plasma glucose (FPG) was measured before and after the treatment. Life-style information was collected by weekly follow-up. Genotyping of the two single-nucleotide polymorphisms was performed using the single base primer extension method. T-test, one-way analysis of variance, and Pearson χ-test were used to evaluate the effects of rs2237892 and rs2237897 on the FPG reduction and treatment success rate. After 8 weeks of gliclazide therapy, the FPG decreased significantly from 10.9±2.8 to 7.4±2.2 mmol/l (P<0.001). Compared with the CC genotype, patients with CT or TT genotypes of rs2237897 achieved greater reduction in FPG (3.9±2.6 vs. 3.2±2.4 mmol/l, P=0.003; 33.9±19.0 vs. 27.7±17.4%, P<0.001) and a higher rate of treatment success (74.1 vs. 65.2%, P=0.042 for criterion 1; 61.1 vs. 44.5%, P<0.001 for criterion 2, respectively), whereas no significant difference was found in the FPG reduction and treatment success rate among different genotypes of rs2237892. Our results indicated that a common variant of KCNQ1, rs2237897, was associated with the efficacy of gliclazide after 8-week monotherapy in Chinese newly diagnosed type 2 diabetic patients. The FPG reduction and treatment success rate were significantly higher in carriers of CT and TT genotypes.

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA1c after 24 weeks. The secondary endpoints were patients achieving HbA1c≤7.0% (53mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA1c at baseline was 8.6% (70mmol/mol) in both groups. At week 24, the adjusted mean HbA1c levels decreased by −1.19% (−13.09mmol/mol) with vildagliptin add-on and −0.46% (−5.06mmol/mol) with sulfonylurea (P<0.001). Significantly more vildagliptin add-on patients achieved HbA1c≤7.0% (53mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137).

Comparison of the effects of Roux-en-Y gastrojejunostomy and LRYGB with small stomach pouch on type 2 diabetes mellitus in patients with BMI

BackgroundObjective: Based on distinct epidemiologic features of Chinese type 2 diabetes mellitus (T2DM) patients, who tend to have abdominal fat deposition, but with normal or mildly overweight epidemiologic features, our center initially had treated T2DM with body mass index (BMI)<35 kg/m² by performing laparoscopic Roux-en-Y gastrojejunostomy since 2008. This procedure is successful in treating abnormal glucose metabolism but not in improving abdominal visceral obesity. However, since 2011, laparoscopic Roux-Y gastric bypass (LRYGB) with a small stomach pouch has been performed at our center, with prominent resolution of abdominal visceral obesity and lower incidences of postoperative complications. The purpose of the present study was to formally compare these different procedures. MethodsFrom 2011 to 2013, 60 patients who met the NIH criteria were recruited and randomly assigned to undergo either laparoscopic Roux-en-Y gastrojejunostomy (n = 30) or LRYGB with a small stomach pouch (n = 30). All of the patients were followed for 12 months, and pre- and postoperative changes in BMI, waist circumference, fasting plasma glucose (FPG), postprandial plasma glucose (PBG), glycated hemoglobin (HbA1c), homoeostatic model assessment (HOMA-IR), the body fat rate and major complications were recorded. ResultsBoth procedures were successful in reducing HbA1c, FPG, and PBG levels and HOMA-IR scores. However, LRYGB with a small stomach pouch resulted in a greater reduction in FPG, PBG, and HbA1c levels, and HOMA-IR scores compared with Roux-en-Y gastrojejunostomy. In addition, the reductions in BMI, body fat content, waist circumference, and the incidence of postoperative marginal ulcers in the small-stomach-pouch LRYGB were significant. ConclusionsBoth procedures are effective treatments for T2DM patients with BMI<35 kg/m². However, the advantages of resolved abnormal glucose metabolism and abdominal visceral obesity and decreased incidences of surgical complications are more obvious for LRYGB with a small gastric pouch. Potentially, LRYGB with a small gastric pouch is more suitable for Chinese diabetic patients with BMI <35 kg/m².

Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: Results of a randomized controlled trial

AimThis study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. MethodsThe randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000mg twice daily) SPC compared with a sitagliptin/metformin (50/1000mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000–2000mg/day). ResultsThe change in FPG from baseline to day 14 was significantly greater (P<0.02, Wilcoxon) with vildagliptin [–21.9mg/dL (SD 27.0)] than with sitagliptin [–14.5mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P<0.05, Wilcoxon). ConclusionBoth of these DPP-4 inhibitors, given as SPCs twice daily with metformin, lowered FPG after 14 days of treatment. However, vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance.

Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials.

IntroductionInsulin degludec (degludec) is a basal insulin with an ultra-long, stable action profile and reduced pharmacodynamic variability. Seven phase 3a trials compared degludec with insulin glargine (glargine). Patient-level meta-analyses were performed to obtain a comprehensive overview of differences between the insulin preparations, possible because consistent outcome definitions were utilized.MethodsThree categories of trials were analyzed: basal–bolus-treated type 1 diabetes mellitus (T1DMB/B), insulin-naïve type 2 diabetes mellitus (T2DMinsulin-naïve), and basal–bolus-treated T2DM (T2DMB/B). Regression models were adjusted for baseline characteristics. Endpoints analyzed were glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), insulin dose and hypoglycemic rates analyzed in mutually exclusive groups: non-severe nocturnal, non-severe daytime, and severe.ResultsAs with previous treat-to-target trials, reductions in HbA1c were similar between degludec and glargine. Reductions in FPG were significantly greater with degludec in T1DMB/B and T2DMinsulin-naïve. Total daily insulin dose was significantly lower with degludec in T1DMB/B and T2DMinsulin-naïve. Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DMB/B, T2DMinsulin-naïve and T2DMB/B, respectively: non-severe nocturnal 0.83, 0.64, 0.75 (all P < 0.05); non-severe daytime 1.14 [not significant (ns)], 0.89 (ns), and 0.83 (P < 0.05). Rate ratios for severe events were 1.12 (ns) (T1DMB/B); 0.14 (P < 0.05) (T2DMinsulin-naïve); and not analyzed (T2DMB/B) due to too few events.ConclusionsCompared with glargine, degludec is associated with equivalent HbA1c control and significantly lower nocturnal hypoglycemia rates. In T1DMB/B and T2DMinsulin-naïve, degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0076-9) contains supplementary material, which is available to authorized users.

Effect of gender on treatment outcomes in type 2 diabetes mellitus

AimTo evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy. MethodsThis is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment. ResultsOverall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c≤7.0% (53mmol/mol) (54.3% vs 60.8%, respectively, p=0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p=0.4625). Females had significantly greater reductions in FPG (3.1mg/dL, p=0.0458), required significantly higher insulin doses (0.03IU/kg, p=0.0071), and had significantly higher annual rates of symptomatic (p<0.0001), glucose-confirmed (<50 and <70mg/dL) symptomatic (p=0.0005 and p<0.0001), and severe hypoglycemia (p=0.0020) than males. ConclusionsFemales in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.

Less Nocturnal Hypoglycemia for Insulin Degludec vs. Insulin Glargine in Subjects with T1DM and Baseline A1c of 7.5–8.5%: A Meta-Analysis

The risk of hypoglycemia increases as A1c levels approach recommended targets. Insulin degludec (IDeg) is a new basal insulin that forms soluble multi-hexamers upon injection, resulting in an ultra-long action profile. We analyzed whether IDeg allows improved glycemic control together with lower rates of hypoglycemia vs. insulin glargine (IGlar) in T1DM patients with baseline A1c 7.5–8.5%. Changes in A1c and fasting plasma glucose (FPG) and rates of hypoglycemia were analyzed with linear models. Hypoglycemia was defined as rates of self-reported confirmed hypoglycemia (PG<[3.1 mmol/L] 56 mg/dL or severe episodes requiring assistance) and nocturnal confirmed hypoglycemia (onset 00:01–05:59h, inclusive). The analysis included all open-labeled randomized treat-to-target phase 3a trials in T1DM, where IDeg (n=223) and IGlar (n=109) were dosed once daily in a basal–bolus regimen. A1c decreased from 8.0% at baseline in both groups to 7.6 vs. 7.5% for IDeg vs. IGlar, respectively (treatment difference: 0.05 [–0.12;0.22] 95% CI). FPG decreased from 9.7 to 7.9 mmol/L for IDeg vs. 9.8 to 9.1 mmol/L for IGlar (treatment difference: –1.01 mmol/L [–1.95;–0.08] 95% CI). There was no difference in overall hypoglycemia or severe hypoglycemia. Despite the lower FPG achieved with IDeg, the rate of nocturnal hypoglycemia was lower with IDeg compared to IGlar (rate ratio: 0.68 [0.50;0.93] 95% CI). In conclusion, for patients with T1DM and baseline A1c of 7.5–8.5%, treatment with IDeg results in comparable improvement in A1c with significantly lower rate of nocturnal hypoglycemia (32%) and greater reduction in FPG compared to IGlar.

Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes

To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug-naÏve patients with type 2 diabetes. After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized in a double-blind manner to initial treatment with a FDC of sitagliptin/metformin 50/500 mg twice daily (N = 261) or pioglitazone 30 mg per day (N = 256). Sitagliptin/metformin and pioglitazone were up-titrated over 4 weeks to doses of 50/1000 mg twice daily and 45 mg per day, respectively. Both treatments were then continued for an additional 28 weeks. From a mean baseline HbA1c of 8.9% in both groups, least squares (LS) mean changes in HbA1c at week 32 were -1.9 and -1.4% for sitagliptin/metformin and pioglitazone, respectively (between-group difference = -0.5%; p < 0.001). A greater proportion of patients had an HbA1c of <7% at week 32 with sitagliptin/metformin vs. pioglitazone (57% vs. 43%, p < 0.001). Compared with pioglitazone, sitagliptin/metformin treatment resulted in greater LS mean reductions in fasting plasma glucose (FPG) [-56.0 mg/dl (-3.11 mmol/l) vs. -44.0 mg/dl (-2.45 mmol/l), p < 0.001] and in 2-h post-meal glucose [-102.2 mg/dl (-5.68 mmol/l) vs. -82.0 mg/dl (-4.56 mmol/l), p < 0.001] at week 32. A substantially greater reduction in FPG [-40.5 mg/dl (-2.25 mmol/l) vs. -13.0 mg/dl (-0.72 mmol/l), p < 0.001] was observed at week 1 with sitagliptin/metformin vs. pioglitazone. A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of β-cell function (HOMA-β) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin. Both sitagliptin/metformin and pioglitazone were generally well tolerated. Sitagliptin/metformin led to weight loss (-1.4 kg), while pioglitazone led to weight gain (3.0 kg) (p < 0.001 for the between-group difference). Higher incidences of diarrhoea (15.3% vs. 4.3%, p < 0.001), nausea (4.6% vs. 1.2%, p = 0.02) and vomiting (1.9% vs. 0.0%, p = 0.026), and a lower incidence of oedema (1.1% vs. 7.0%, p < 0.001), were observed with sitagliptin/metformin vs. pioglitazone. The between-group difference in the incidence of hypoglycaemia did not reach statistical significance (8.4 and 4.3% with sitagliptin/metformin and pioglitazone, respectively; p = 0.055). Compared with pioglitazone, initial therapy with a FDC of sitagliptin and metformin led to significantly greater improvement in glycaemic control as well as a higher incidence of prespecified gastrointestinal adverse events, a lower incidence of oedema and weight loss vs. weight gain.

Treatment with insulin detemir or NPH insulin in children aged 2-5 yr with type 1 diabetes mellitus

This randomised (1:1), multinational, open-labelled, parallel group trial compared insulin detemir (IDet) with neutral protamine Hagedorn (NPH) insulin, in combination with mealtime insulin aspart, over 1 yr in subjects aged 2-16 yr with type 1 diabetes mellitus. Of 348 randomised subjects, 82 (23.6%) were 2-5 yr (IDet: 42, NPH: 40). This article is a descriptive subgroup analysis of these young children. Baseline characteristics (IDet vs. NPH) were similar: mean age, 4.3 vs. 4.5 yr; diabetes duration, 2.2 vs. 2.1 yr; males, 42.9 vs. 52.5%. Mean haemoglobin A1c (HbA1c) was similar between groups at baseline (8.2 vs. 8.1%), and changed little over 1 yr (8.1 vs. 8.3%). Fasting plasma glucose (FPG) was similar at baseline (8.44 vs. 8.56 mmol/L) and decreased during the study (-1.0 vs. -0.45 mmol/L). A lower rate of hypoglycaemia was observed with IDet compared with NPH (24-h; 50.6 vs. 78.3 episodes per patient-year; nocturnal hypoglycaemia, 8.0 vs. 17.4 episodes per patient-year). No severe hypoglycaemic episodes occurred with IDet, while 3 subjects reported 6 episodes with NPH. Change in weight standard deviation score standardised by age and gender was -0.17 with IDet and +0.03 with NPH. A slightly lower proportion of subjects in this age group reported adverse events with IDet than with NPH (69.0 vs. 77.5%). Serious adverse events were few (5 with IDet, 7 with NPH). In conclusion, long-term treatment with IDet in children aged 2-5 yr suggested similar glycaemic control, greater reduction in FPG, lower rates of hypoglycaemia, no inappropriate weight gain, and fewer adverse events compared with NPH.

Basal-bolus therapy with insulin detemir using the 303 algorithm in the US PREDICTIVE 303 trial

The aim of this study was to compare a simplified patient-driven algorithm (303 Algorithm) to physician-driven adjustments in a subset of 193 patients with type 2 diabetes from the PREDICTIVE 303 study who were using basal-bolus insulin therapy. PREDICTIVE 303 was a 26-week, randomized, phase 4 study, in which subjects were either instructed to adjust their insulin detemir dose every 3 days by +/-3 units if mean fasting plasma glucose (FPG) values were above 110 mg/dL or below 80 mg/dL (303 Algorithm), or had physicians adjust the insulin detemir dose according to usual practice (Standard-of-care). Patients in both groups achieved similar reductions in glycated hemoglobin (-0.2% and -0.3% for 303 Algorithm and Standard-of care groups, respectively; between groups P=0.60). 303 Algorithm group patients achieved a greater reduction in FPG (-21.3 mg/dL vs. 0.2 mg/dL; between groups P=0.03). Both 303 Algorithm and Standard-of care groups experienced a similar rate of overall hypoglycemia, and similar weight reduction (-1.7 kg and -0.4 kg, respectively; between groups P=0.07). Over 82% of patients in both groups used insulin detemir once daily. Adjustments of a once-daily detemir dose by patients using the 303 Algorithm in a basal-bolus setting is equally effective in improving glycemic control in patients with type 2 diabetes compared with physician-directed basal dose adjustments.

Improving glycemic control with insulin detemir using the 303 Algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study

PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80 mg/dL, reduce dose by 3 units; between 80-110mg/dL, no change; > 110mg/dL, increase by 3 units. Physicians adjusted the detemir dose for patients in the Standard-of-care group according to their usual practice. No control insulin was used for comparison to insulin detemir.Reductions in glycosylated hemoglobin (HbA(1c)) from baseline were similar between those patients in the 303 Algorithm and Standard-of-care groups (-1.1 and -1.0%, respectively; between group p = 0.0933); patients in the 303 Algorithm group achieved a greater reduction in FPG. Patients in both groups experienced a similar, low rate of hypoglycemia. Over 95% and 92% of patients, respectively, used detemir once daily.These data indicate that patients with type 2 diabetes naïve to insulin can effectively implement the 303 Algorithm to initiate and adjust a once-daily dose of insulin detemir to achieve improvements in glycemic control.

Improving glycemic control with insulin detemir using the 303 Algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study

ABSTRACTObjective: PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.Methods: Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80mg/dL, reduce dose by 3 units; between 80–110 mg/dL, no change; >110 mg/dL, increase by 3 units. Physicians adjusted the detemir dose for patients in the Standard-of-care group according to their usual practice. No control insulin was used for comparison to insulin detemir.Results: Reductions in glycosylated hemoglobin (HbA1c) from baseline were similar between those patients in the 303 Algorithm and Standard-of-care groups (−1.1 and −1.0%, respectively; between group p = 0.0933); patients in the 303 Algorithm group achieved a greater reduction in FPG. Patients in both groups experienced a similar, low rate of hypoglycemia. Over 95% and 92% of patients, respectively, used detemir once daily.Conclusion: These data indicate that patients with type 2 diabetes naïve to insulin can effectively implement the 303 Algorithm to initiate and adjust a once-daily dose of insulin detemir to achieve improvements in glycemic control.

Effect of Glyburide—Metformin Combination Tablet in Patients with Type 2 Diabetes

To evaluate the efficacy and safety of glyburide/metformin combined tablet compared to glyburide or metformin alone in patients with type 2 diabetes. In this 16-week, multicenter, randomized, double-blind, 4-arm and parallel clinical trial study, 100 patients with type 2 diabetes mellitus were recruited and 76 patients were available for statistical analysis at the end of the study. After 1 week of placebo washout period, eligible patients were randomly assigned into 1 of 4 treatment groups: glyburide 5 mg b.i.d.; metformin 500 mg b.i.d.; glyburide/metformin 2.5 mg/500 mg b.i.d.; or glyburide/metformin 5.0 mg/500 mg b.i.d. The doses were titrated every 2 weeks to a maximum of 4 tablets per day if the patients fasting plasma glucose (FPG) still exceeded 140 mg/dL. Efficacy was evaluated by the changes from baseline in glycosylated hemoglobin (HbA1c) and FPG at week 16. Adverse events were recorded and summarized by treatment group. At week 16, patients who received glyburide/metformin 2.5 mg/500 mg or 5.0 mg/500 mg tablets had greater reductions in FPG (all p<0.001) compared with glyburide or metformin monotherapy. Patients who took glyburide/ metformin 2.5 mg/500 mg tablet and glyburide/metformin 5.0 mg/500 mg tablet had significant decreases in HbA1c (both p<0.0125). Furthermore, treatment with glyburide/metformin 2.5 mg/500 mg resulted in significantly greater reduction in HbA1c compared to glyburide or metformin (-1.77%, p<0.001 and -1.34%, p=0.002), and treatment with glyburide/metformin 5.0 mg/500 mg resulted in significant lowering of HbA1c compared to glyburide or metformin alone (-1.73%, p<0.001 and -1.30%, p=0.005). Both the glyburide/metformin 2.5 mg/500 mg and glyburide/metformin 5.0 mg/500 mg combination therapy groups experienced fewer gastrointestinal adverse events than the metformin monotherapy group. Both glyburide/metformin 2.5 mg/500 mg and glyburide/metformin 5.0 mg/500 mg combination therapy were efficacious and well tolerated in the treatment of Chinese patients with type 2 diabetes mellitus.

Glycemic Effects of Moderate Alcohol Intake Among Patients With Type 2 Diabetes

In a randomized controlled trial, we assessed the effect of daily moderate alcohol intake on glycemic control in the fasting and postprandial states in patients with type 2 diabetes who previously had abstained from alcohol. We randomly assigned 109 patients (41-74 years old) with established type 2 diabetes who abstained from alcohol to receive 150 ml wine (13 g alcohol) or nonalcoholic diet beer (control) each day during a 3-month multicenter trial. The beverages were consumed during dinner. Diet and alcohol consumption were monitored. During the intervention, 17% of participants (12% from the alcohol group) dropped out, leaving 91 who completed the trial. Within the alcohol group, fasting plasma glucose (FPG) decreased from 139.6 +/- 41 to 118.0 +/- 32.5 mg/dl after 3 months compared with 136.7 +/- 15.4 to 138.6 +/- 27.8 mg/dl in the control subjects (P(v) = 0.015). However, alcohol consumption had no effect on 2-h postprandial glucose levels (difference of 18.5 mg/dl in the control group vs. 17.7 mg/dl in the alcohol group, P(v) = 0.97). Patients in the alcohol group with higher baseline A1C levels had greater reductions in FPG (age-adjusted correlation -0.57, P(v) < 0.001). No significant changes were observed in the levels of bilirubin, alkaline phosphatase, alanine aminotransferase, or aspartate aminotransferase, and no notable adverse effects were reported. Participants in the alcohol group reported an improvement in the ability to fall asleep (P(v) < 0.001). Among patients with type 2 diabetes who had previously abstained from alcohol, initiation of moderate daily alcohol consumption reduced FPG but not postprandial glucose. Patients with higher A1C may benefit more from the favorable glycemic effect of alcohol. Further intervention studies are needed to confirm the long-term effect of moderate alcohol intake.

Comparative Efficacy and Potency of Long-Term Therapy with Glipizide or Glyburide in Patients with Type 2 Diabetes Mellitus

Long-term studies on the comparative efficacy and relative potency of glipizide and glyburide are sparse and controversial. In a randomized prospective trial, we compared the effectiveness and relative potency of glipizide and glyburide over a 15-month period in 18 patients with type 2 diabetes mellitus (DM2) (9 on glyburide and 9 on glipizide) who were unresponsive to diet therapy. Glycemic control was assessed using 4 methods: 1) quarterly fasting plasma glucose (FPG), and 2-hour postprandial plasma glucose after a standard breakfast; 2) insulin and glucose response to Sustacal (test meal) challenge every 3 to 6 months; 3) quarterly hemoglobin A1c; and 4) intravenous glucose tolerance testing every 6 months to measure first and second phase insulin secretion. Patient characteristics were similar in each treatment group. Similar doses of glipizide (11 mg/day) or glyburide (10 mg/day) resulted in comparable reduction of FPG and hemoglobin A1c and increase in first phase insulin response to intravenous glucose tolerance testing. There was greater reduction in FPG and 2-hour postprandial plasma glucose with glipizide than with glyburide in 6 months. Contrary to the Physicians' Desk Reference, but consistent with another short-term study, our long-term study demonstrated that glipizide and glyburide are equipotent at similar doses in controlling hyperglycemia in DM2. Glipizide and glyburide are effective in controlling hyperglycemia with similar doses in DM2. Glipizide exhibits greater reduction in FPG and 2PPG at 6 months. Additional studies are needed to validate equipotency of these drugs.

Comparative Efficacy and Potency of Long-Term Therapy with Glipizide or Glyburide in Patients with Type 2 Diabetes Mellitus

Background: Long-term studies on the comparative efficacy and relative potency of glipizide and glyburide are sparse and controversial. Methods: In a randomized prospective trial, we compared the effectiveness and relative potency of glipizide and glyburide over a 15-month period in 18 patients with type 2 diabetes mellitus (DM2) (9 on glyburide and 9 on glipizide) who were unresponsive to diet therapy. Glycemic control was assessed using 4 methods: 1) quarterly fasting plasma glucose (FPG), and 2-hour postprandial plasma glucose after a standard breakfast; 2) insulin and glucose response to Sustacal (test meal) challenge every 3 to 6 months; 3) quarterly hemoglobin Ale; and 4) intravenous glucose tolerance testing every 6 months to measure first and second phase insulin secretion. Patient characteristics were similar in each treatment group. Results: Similar doses of glipizide (11 mglday) or glyburide (10 mglday) resulted in comparable reduction of FPG and hemoglobin Ale and increase in first phase insulin response to intravenous glucose tolerance testing. There was greater reduction in FPG and 2-hour postprandial plasma glucose with glipizide than with glyburide in 6 months. Contrary to the Physicians’ Desk Reference, but consistent with another short-term study, our long-term study demonstrated that glipizide and glyburide are equipotent at similar doses in controlling hyperglycemia in DM2. Conclusions: Glipizide and glyburide are effective in controlling hyperglycemia with similar doses in DM2. Glipizide exhibits greater reduction in FPG and 2PPG at 6 months. Additional studies are needed to validate equipotency of these drugs.