Glibenclamide Improves the Response to Insulin Treatment in Non-insulin-dependent Diabetics with Second Failure to Sulfonylurea Therapy

ABSTRACT The effect of combined insulin-glibenclamide therapy on glucose control was evaluated in a double-blind placebo controlled study of 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and second failure to oral antidiabetic therapy with glibenclamide or glipizide. After an observation period of 1–3 months, insulin treatment was initiated which resulted in rapid improvement of the glycemic control within 6 weeks. Thereafter glibenclamide or placebo was added to insulin for a further 12 weeks. Glibenclamide improved the glycemic control as expressed by a diminution of blood glucose and HbA_1c. This was observed in spite of the fact that the daily insulin dose was reduced by approximately 30% in the glibenclamide-treated group of patients. It is concluded that in NIDDM patients with second failure to glibenclamide ot glipizide therapy, the responsiveness to glibenclamide may be at least partially restored by a short period of insulin treatment. It is suggested that therapy with insulin and glibenclamide is an appropriate treatment regimen for NIDDM patients with second failure to sulfonylurea therapy.     

Short-term metabolic effects of the ACE-inhibitor benazepril in type 2 diabetes mellitus associated with arterial hypertension.

To assess the short-term metabolic effects a long-acting non-sulphydryl ACE-inhibitor benazepril on glycaemic control in Type 2 diabetes mellitus and arterial hypertension, 10 hypertensive diabetic patients treated with glibenclamide were studied in a double-blind, crossover fashion over two 10-day periods in which either benazepril (10 mg/day) or placebo was given. At the end of the 10 day treatment, both blood pressure and plasma glucose concentrations were lower after benazepril versus placebo (benazepril, blood pressure: 143 +/- 11/83 +/- 5 mmHg, plasma glucose: 7.1 +/- 1.2 mmol/l; placebo: blood pressure: 157 +/- 10/99 +/- 2 mmHg, plasma glucose: 8.2 +/- 1 mmol/l, p < 0.05). In response to an oral glucose tolerance test combined with 1 mg intravenous glibenclamide, plasma glucose levels were lower after benazepril versus placebo (0-460 min: 8.4 +/- 0.8 versus 10.5 +/- 0.9 mmol/l, p < 0.05), whereas plasma insulin, C-peptide and glibenclamide concentrations were not different. It is concluded that a short-term administration of benazepril in Type 2 diabetes mellitus reduces blood pressure and improves blood glucose control, most likely by decreasing insulin resistance.     

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.     

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients

Aim: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes.
Methods: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m²), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose ( n  = 25) or 1 mg t.i.d. glibenclamide ( n  = 27) or one t.i.d. placebo ( n  = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test.
Results: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0].
Conclusions: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.     

Insulin lispro (Lys(B28), Pro(B29) in the treatment of diabetes during the fasting month of Ramadan. Ramadan Study Group.

AIMS: To compare insulin lispro with soluble human insulin in patients with Type 2 diabetes mellitus fasting during Ramadan, with respect to the rate of hypoglycaemic episodes and postprandial blood glucose values after the main meal after sunset. METHODS: The insulins were compared in an open-label, randomized, cross-over study of 70 outpatients. Hypoglycaemic episodes were recorded by the patients in a self-monitoring diary. Fasting, 1-h and 2-h postprandial blood glucose values were recorded by the patient on three consecutive days at the end of each treatment period. RESULTS: The fasting blood glucose values before sunrise (P>0.4) and after sunset (P>0.6) were similar and did not differ significantly between both treatment groups. The rise in blood glucose after the main meal after sunset was 3.0+/-0.4 mmol/l after 1 h in the insulin lispro treatment group compared to 4.3+/-0.4 mmol/l in the soluble insulin treatment group (P<0.01), and 2.6+/-0.4 mmol/l after 2h with insulin lispro compared to 4.0+/-0.5 mmol/l with soluble insulin (P<0.008). Mean hypoglycaemic episodes per patient over 14 days were 1.3+/-0.1 vs. 2.6+/-0.2, P<0.002, respectively, for insulin lispro and soluble insulin. Most hypoglycaemic episodes occurred during the time period from 6 h after the before sunrise meal until breaking the fast after sunset. CONCLUSIONS: The significantly lower rate of hypoglycaemic episodes combined with better control of postprandial blood glucose suggest insulin lispro may be more suitable prandial insulin for patients treated with Type 2 diabetes who fast during Ramadan.     

Improved glycaemic control with miglitol in inadequately-controlled type 2 diabetics

OBJECTIVE: The study compared the long-term efficacy and safety of miglitol to placebo in Type 2 diabetic outpatients inadequately controlled on combination therapy of diet, glibenclamide and metformin. METHODS: Type 2 diabetic patients (n = 154) receiving glibenclamide 7-20 mg/day and at least one 500-850 mg tablet metformin per day were randomized to receive additional miglitol or placebo for 24 weeks, titrated up stepwise from 25 to 100 mg trice daily. RESULTS: Addition of miglitol to sulphonylureas and metformin (per protocol analysis) produced a statistically, significantly greater reduction in HbA1c (-0.55%, P = 0.04) and postprandial glucose (-2.6 mmol/l, P = 0.0009) from baseline to endpoint than placebo (-0.2% and -0.6 mol/l, respectively). Reduction in fasting blood glucose was greater with miglitol than placebo, and there was a possible difference in favor of miglitol for fasting and postprandial triglyceride levels, but these did not reach statistical significance. Flatulence and diarrhea were reported by statistically, significantly more patients receiving miglitol than placebo, but adverse events overall were reported by only 10% more patients in the miglitol group. No cases of hypoglycaemia were reported. CONCLUSIONS: Miglitol can safely and effectively be added to long-term combination therapy in people with Type 2 diabetes inadequately controlled with glibenclamide plus metformin.     

The blood glucose lowering effects of exercise and glibenclamide in patients with Type 2 diabetes mellitus

Physical exercise is associated with a fall in serum insulin levels, whereas sulphonylurea administration increases insulin release. To date, the opposing effects of exercise and sulphonylurea administration have not been systematically studied in Type 2 diabetic patients, who are not infrequently treated with sulphonylureas. In this study nine patients with Type 2 diabetes mellitus were subjected to four treatments in random order on separate days: (A) endurance exercise after the administration of 3.5 mg glibenclamide; (B) as A but given only 1.75 mg glibenclamide; (C) as A but with placebo; (D) rest and administration of 1.75 mg glibenclamide. Exercise and placebo resulted in only a small decrease in glycaemia. Rest and administration of 1.75 mg glibenclamide led to a moderate but steady fall in blood glucose concentrations. If glibenclamide administration and exercise were combined, blood glucose concentrations declined more markedly. Serum insulin concentrations showed a physiological decrease during exercise and placebo administration. If patients rested after administration of glibenclamide serum insulin levels rose and remained elevated. When exercise and glibenclamide were combined the rise in serum insulin levels was blunted and insulin levels fell once exercise was begun. Thus, exercise attenuates the glibenclamide induced increase in serum insulin in moderately hyperglycaemic Type 2 diabetic patients. Nevertheless, exercise has a substantial hypoglycaemic effect in glibenclamide treated Type 2 diabetic patients. © 1998 John Wiley & Sons, Ltd.     

A double blind study of the effect of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus.

Hyperlipidaemia, in particular raised concentrations of serum triglycerides, together with raised plasma non-esterified fatty acid concentrations, is common in patients with Type 2 (non-insulin-dependent) diabetes mellitus and may be associated with insulin insensitivity. Thirty non-obese Type 2 diabetic patients (15 controlled with diet alone and 15 with diet plus oral sulphonylurea therapy) were therefore recruited to take part in a double-blind, randomized, crossover comparison of acipimox (250 mg three times daily for 3 months) and placebo. Serum lipids, blood glucose control, insulin sensitivity, and glucose tolerance were measured before and after each treatment period. There was a significant decrease in serum triglycerides (2.05 +/- 1.08 vs 2.91 +/- 1.75: p < 0.005), cholesterol (5.66 +/- 1.02 vs 6.26 +/- 1.17: p = 0.0005), and apoprotein B (1.32 +/- 0.23 vs 1.44 +/- 0.25: p < 0.05) while HDL cholesterol and apoprotein A-1 concentrations were unchanged. There was no change in blood glucose control measured by fasting glucose, insulin, and HBA, concentrations, but there was a significant improvement in insulin action assessed by glucose-insulin infusion. Although plasma non-esterified fatty acid concentrations were lower during the oral glucose tolerance test after acipimox, there was no difference in either the peak or 2-h plasma glucose concentrations and the total area under the glucose curve did not change. Acipimox was well tolerated and no patients withdrew from the study for drug-related symptoms. Thus, acipimox effectively lowers serum cholesterol and triglycerides in patients with Type 2 diabetes without adversely altering blood glucose control, and appears to improve insulin sensitivity.     

Insulin therapy in type 2 diabetes: what is the evidence?

Aim: To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus Methods: A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. Results: The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long‐acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long‐acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long‐acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal–bolus regimen seems not possible. Some studies showed that rapid‐acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. Conclusion: A once‐daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.     

How Does Glibenclamide Lower Plasma Glucose Concentration in Patients with Type 2 Diabetes?

Twelve patients with Type 2 diabetes and uncontrolled hyperglycaemia, never before treated with anti-diabetic drugs, were studied before and after several months of glibenclamide therapy. Fasting plasma glucose fell significantly (p less than 0.01) from 12.5 +/- 1.1 (mean +/- SE) to 8.3 +/- 0.4 mmol l-1 with glibenclamide therapy, as did glycosylated haemoglobin (from 12.0 +/- 0.9 to 8.4 +/- 0.7%). The improvement in blood glucose control was accompanied by an increase in postprandial plasma insulin concentration measured hourly from 0800 to 1600 h (p less than 0.001). Over the same period, plasma NEFA and lactate levels were significantly (p less than 0.001) lower after treatment with glibenclamide. Mean (+/- SE) insulin-mediated glucose metabolic clearance rate was evaluated during glucose clamp studies, and was significantly higher (p less than 0.001) after glibenclamide therapy at steady-state insulin levels of approximately 10 mU l-1 (53 +/- 3 vs 38 +/- 2 ml-2 min-1) and approximately 70 mU l-1 (78 +/- 9 vs 55 +/- 6 ml m-2 min-1). Hepatic glucose production was also lower following glibenclamide treatment at both the lower (56 +/- 5 vs 68 +/- 5 mg m-2 min-1) and higher 22 +/- 4 vs 32 +/- 6 mg m-2 min-1) insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

The lipoprotein profile differs during insulin treatment alone and combination therapy with insulin and sulphonylureas in patients with Type 2 diabetes mellitus.

AIMS: To study whether changes in endogenous insulin secretion at the same glycaemic control affect the plasma concentrations of lipoproteins in patients with Type 2 diabetes mellitus. METHODS: Fifteen patients, age 59+/-2 years (mean +/- SEM), body weight 86.3+/-3.0kg, body mass index 29.6+/-0.9 kg/m2 were treated with sulphonylurea and insulin in combination or with insulin alone in a randomized, double-blind, crossover study. All patients were treated with a multiple daily injection regimen with the addition of glibenclamide 10.5 mg daily or placebo tablets. RESULTS: During combination therapy, the dose of insulin was 25% less (P < 0.002) and there was a 29% increase in plasma C-peptide concentration (P = 0.01). Plasma levels of free insulin were not changed. Plasma levels of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein (IGFBP)-1 were lowered. There were no differences in the 24-h blood glucose profiles or HbA1c (6.0+/-0.2 vs. 6.3+/-0.2%; P = 0.16). Body weight was similar. There was a significant decrease in plasma LDL cholesterol (3.04+/-0.24 vs. 3.41+/-0.21 mmol/l; P = 0.04), apolipoprotein A1 and of lipoprotein(a) but an increase in VLDL-triglycerides (1.36+/-0.31 vs. 0.96+/-0.16 mmol/l; P = 0.02) during combination therapy. The ratio between LDL cholesterol and apolipoprotein B concentrations was significantly lower during combination therapy (P < 0.01). CONCLUSIONS: Combination therapy with insulin and sulphonylureas increases portal insulin supply and thereby alters liver lipoprotein metabolism when compared with insulin therapy alone.     

Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril.

AIMS: The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus. METHODS: Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P). RESULTS: Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed. CONCLUSIONS: An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.     

Insulin plus a sulfonylurea agent for treating type 2 diabetes

PURPOSE: To review the recent literature on the efficacy of combined insulin and sulfonylurea therapy in patients with type 2 diabetes. DATA SOURCES: Pertinent articles were obtained through an English-language MEDLINE search from 1979 to 1990 and from the references of these articles. STUDY SELECTION: We reviewed the studies in which patients with poorly controlled diabetes received insulin and a sulfonylurea agent and in which insulin treatment alone (usually given in conjunction with a placebo) was compared with insulin plus sulfonylurea therapy. DATA EXTRACTION: Pre- and post-treatment insulin doses, blood glucose levels, glycated hemoglobin values, C-peptide levels, and insulin levels were analyzed. Other data were analyzed separately. RESULTS OF DATA SYNTHESIS: Data from similar trials were compared. Data from concurrent trials were analyzed separately from data derived from cross-over trials. Weighted mean fasting blood glucose levels, glycated hemoglobin levels, insulin dosage, and fasting C-peptide concentrations were determined for insulin plus placebo and insulin plus sulfonylurea agent groups for both types of studies. In concurrent trials, the weighted mean post-treatment glycated hemoglobin level was 11.1% after insulin plus placebo compared with 10.0% after insulin plus a sulfonylurea agent. In cross-over trials, the corresponding values were 10.6% and 9.8%. CONCLUSIONS: Combination therapy with insulin and a sulfonylurea agent only slightly improved glycemic control in patients with type 2 diabetes. When a sulfonylurea agent was used, less exogenous insulin was needed, but fasting serum insulin levels were not different between the treatment groups. Such therapy did not produce nearly normal blood glucose concentrations and therefore should not be used in patients with poorly controlled type 2 diabetes receiving insulin.     

Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trial.

OBJECTIVE: To determine the effect of adding nateglinide to therapy with insulin glargine in adults with Type 2 diabetes previously treated with insulin and with poor blood glucose control. RESEARCH DESIGN AND METHODS: In this 16-week, double-blind, placebo-controlled study, people with Type 2 diabetes [n = 55, HbA(1c) 8.2 +/- 1.0 (+/- sd)%, duration of diabetes 12.8 +/- 6.0 years, duration of insulin treatment 6.0 +/- 4.0 years] were transferred to single bedtime injection of insulin glargine for a titration period of 4 weeks, and then randomized to nateglinide or matching placebo before meals in addition to insulin glargine. Metformin was continued if taken. Doses of insulin and oral medication were titrated to protocol for the treatment period of 12 weeks. RESULTS: Baseline-adjusted self-monitored capillary blood glucose concentration at 12 weeks was significantly lower with nateglinide + insulin glargine compared with placebo + insulin glargine after breakfast [difference -2.3 (95% confidence interval -4.4, -0.2) mmol/l, P = 0.030], before lunch [-2.5 (-4.6, -0.3) mmol/l, P = 0.029], and after lunch [-2.3 (-4.3, -0.4) mmol/l, P = 0.021], but not at other times. Baseline-adjusted HbA(1c) was not lower with nateglinide + insulin glargine as compared with placebo + insulin glargine [7.8 +/- 1.4 vs. 8.3 +/- 1.0%, difference -0.43 (-0.98, 0.12)%]. CONCLUSIONS: Addition of nateglinide before meals to once-daily insulin glargine in people with long-standing diabetes already requiring insulin therapy improves blood glucose control in the early part of the day after breakfast and lunch, but does not provide good control of blood glucose levels overall.     

Pre-meal Insulin Analogue Insulin Lispro vs Humulin® R Insulin Treatment in Young Subjects with Type 1 Diabetes

The present prospective one-year randomized study was conducted to compare soluble human insulin, with a new rapid-acting human insulin analogue, lispro, with respect to postprandial glucose excursions, frequency of hypoglycaemic episodes, glucose control, and long-term safety in 39 subjects (20 females, 19 males) with Type 1 diabetes. The duration of diabetes, gender distribution, and age were similar in the two groups. The total number of hypoglycaemic episodes was significantly less (p<0.04, Wilcoxon rank sum test) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period. The 2-h postprandial glucose excursion at 1 year was also significantly less (p<0.05, ANOVA) in the group treated with insulin lispro. The reductions in the total number of hypoglycaemic episodes and in the postprandial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes. However, the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue.     

Insulin combined with Chinese medicine improves glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus

Introduction/Aims

Insufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type 2 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen-Qi-Formula (SQF), a well-known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type 2 diabetes mellitus, and what mechanisms were possibly involved in the treatment.

Materials and Methods

A total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12-week treatment, the fasting blood glucose, postprandial blood glucose, β-cell function, insulin resistance and blood lipids were measured.

Results

The 12 weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but β-cell function and insulin resistance were obviously improved. Furthermore, 12 weeks of treatment with SQF and insulin improved the levels of glucagon-like peptide-1, oxidative stress, blood lipids, coagulation function and bodyweight.

Conclusion

The results from our study showed that the combination therapy of SQF and insulin significantly improved the clinical outcome of type 2 diabetes mellitus compared with insulin monotherapy. The mechanism of improvement was possibly involved in the multiple pathways.     

The effect of pirenzepine on growth hormone and blood glucose levels in type I diabetes mellitus. A controlled study in patients on basal bolus insulin treatment

Increased GH levels in Type I diabetes mellitus have been implicated in the pathogenesis of metabolic complications such as the so-called dawn phenomenon. GH secretion is under control of cholinergic mechanisms. In 21 Type I diabetic patients the effect of oral administration of the anticholinergic drug pirenzepine in addition to intensive insulin therapy on GH and blood glucose levels was studied. At 21.30, 08.00 and 12.00 h, all patients received in random order 50 mg of pirenzepine or placebo po. Blood for determination of GH, blood glucose, cortisol and C-peptide levels were obtained at 3-h intervals. Serum levels of plasma glucose and GH were significantly lower under pirenzepine than under placebo (P less than 0.05 and P less than 0.01, respectively). Serum levels of cortisol, free insulin and C-peptide were comparable on the test and the control day. Our data indicate that in Type I diabetes mellitus the anticholinergic drug pirenzepine is effective in decreasing both GH and blood glucose levels.     

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

Aims/Introduction

Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients.

Materials and Methods

The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed.

Results

Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy.

Conclusions

Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.     

Transient Effect of the Combination of Insulin and Sulfonylurea (Glibenclamide) on Glycemic Control in Non-Insulin Dependent Diabetics Poorly Controlled with Insulin Alone

ABSTRACT In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p<0.001), 24-hour urinary glucose (p<0.01) and glycohemoglobin (HbA₁) concentrations (p<0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p<0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA₁ concentrations (r=0.56, p<0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.     

Efficacy of acarbose in Chinese subjects with impaired glucose tolerance

This multicentre, double-blind, placebo-controlled study investigated the efficacy of acarbose in Chinese individuals with impaired glucose tolerance (determined using a 75 g oral glucose tolerance test). Subjects were randomised to either placebo or acarbose 50 mg t.i.d. for a period of 16 weeks. Primary efficacy variables were the maximum postprandial plasma glucose value (C(max)) and the serum insulin profile. Secondary efficacy parameters included postprandial glucose profile, maximum postprandial insulin concentration (C(max)), changes in lipid profile and blood pressure and HbA(1c) and body weight and conversion to Type 2 diabetes. In the intention-to-treat analysis, acarbose treatment resulted in significantly higher reductions in postprandial glucose and serum insulin concentrations compared to placebo. Triglyceride concentration was the only lipid parameter to be significantly reduced in acarbose subjects. Loss of body weight was also significantly greater for acarbose than placebo subjects. Some 19 individuals converted to Type 2 diabetes (seven acarbose, 12 placebo), but this difference was not significant. Acarbose is efficacious in improving the metabolic state of individuals with impaired glucose tolerance indicating a potential benefit for the delay or prevention of onset of Type 2 diabetes in Chinese subjects.