Insulin glulisine: viewpoints.
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Blood Glucose↗
Biomedical subjects
George Dailey
Publications and source records attributed to George Dailey.
Triple therapy in type 2 diabetes: insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naive patients.
OBJECTIVE: To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-naïve patients with type 2 diabetes inadequately controlled on dual oral therapy with sulfonylurea plus metformin. RESEARCH DESIGN AND METHODS: In this 24-week multicenter, randomized, open-label, parallel trial, 217 patients (HbA(1c) [A1C] 7.5-11%, BMI >25 kg/m(2)) on > or =50% of maximal-dose sulfonylurea and metformin received add-on insulin glargine 10 units/day or rosiglitazone 4 mg/day. Insulin glargine was forced-titrated to target fasting plasma glucose (FPG) < or =5.5-6.7 mmol/l (< or =100-120 mg/dl), and rosiglitazone was increased to 8 mg/day any time after 6 weeks if FPG was >5.5 mmol/l. RESULTS: A1C improvements from baseline were similar in both groups (-1.7 vs. -1.5% for insulin glargine vs. rosiglitazone, respectively); however, when baseline A1C was >9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 0.05). Insulin glargine yielded better FPG values than rosiglitazone (-3.6 +/- 0.23 vs. -2.6 +/- 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 +/- 26 IU vs. 7.1 +/- 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose <3.9 mmol/l (<70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528). The calculated average rate per patient-year of a confirmed hypoglycemic event (<70 mg/dl), after adjusting for BMI, was 7.7 (95% CI 5.4-10.8) and 3.4 (2.3-5.0) for the insulin glargine and rosiglitazone groups, respectively (P = 0.0073). More patients in the insulin glargine group had confirmed nocturnal hypoglycemia of <3.9 mmol/l (P = 0.02) and <2.8 mmol/l (P < 0.05) than in the rosiglitazone group. Effects on total cholesterol, LDL cholesterol, and triglyceride levels from baseline to end point with insulin glargine (-4.4, -1.4, and -19.0%, respectively) contrasted with those of rosiglitazone (+10.1, +13.1, and +4.6%, respectively; P < 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P < 0.05). Insulin glargine had less weight gain than rosiglitazone (1.6 +/- 0.4 vs. 3.0 +/- 0.4 kg; P = 0.02), fewer adverse events (7 vs. 29%; P = 0.0001), and no peripheral edema (0 vs. 12.5%). Insulin glargine saved $235/patient over 24 weeks compared with rosiglitazone. CONCLUSIONS: Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was > or =9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.
Adult↗
Insulin secretagogues: who, what, when, and how?
Sulfonylurea compounds were the first available oral antidiabetic agents and they remain an important tool in our quest for optimal glycemic control. The more recent introduction of meglitinides offers an approach to short-term insulin release with minimal hypoglycemic risk during fasting periods. Published trials suggest that individuals with a hemoglobin A(1c) above 8.5% are unlikely to reach currently recommended targets (6.5% to 7%) without the use of one of these insulin secretagogues. Starting and probable maximally effective doses for glimepiride are 1 to 2 mg initially and 4 mg thereafter. For glyburide and glipizide, these are 2.5 to 5 mg initially, and 10 mg effective at a maximum. The large majority of the effect can be seen within a week, making them very attractive when rapid lowering of glucose is needed. An understanding of the principles will facilitate more effective use of initial and combination therapy.
Administration, Oral↗
Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes.
OBJECTIVE: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS: Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively. CONCLUSIONS: These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.
Blood Glucose↗
Advances in diabetes for the millennium: understanding insulin resistance.
Type 2 diabetes is a heterogeneous disorder in which both insulin resistance and impaired insulin secretion play important roles. Studies in monozygotic twins in which one is discordant for type 2 diabetes and studies of first-degree relatives of patients with type 2 diabetes who still have normal glucose tolerance indicate that impaired insulin secretion can be detected before insulin resistance, suggesting that impaired beta-cell function may be the primary genetic defect. The insulin resistance found in most individuals with impaired glucose tolerance and/or type 2 diabetes appears to be largely acquired and can be accounted for by obesity, physical inactivity, and glucose and lipotoxicity. Progressive deterioration in beta-cell function as demonstrated in the United Kingdom Prospective Diabetes Study (UKPDS) and/or worsening of insulin resistance leads to deterioration in glucose tolerance and to secondary failure of oral antidiabetic drugs. Therefore, agents that improve beta-cell function (such as sulfonylureas and meglitinides) and insulin sensitizers (such as metformin and thiazolidinediones) both are useful alone or in combination for treating type 2 diabetes.
Diabetes Mellitus, Type 2↗
New strategies for basal insulin treatment in type 2 diabetes mellitus.
BACKGROUND: The clinical progression of type 2 diabetes mellitus (DM) is well understood. Glycemic control gradually deteriorates, and progression of DM eventually leads to an increased risk for microvascular and macrovascular complications. Reassessment of current insulin treatment strategies leading to restoration of glycemic control is essential to prevent or stop the progression of type 2 DM and its complications. OBJECTIVE: The purpose of this article was to review the importance of instituting a strategy of basal insulin therapy in patients with type 2 DM. METHODS: Relevant articles were obtained through an online search of PubMed and MEDLINE for literature published from 1990 to 2003. The search terms used were insulin therapy, combination oral therapy, treatment failure, glycemic control, insulin analogues, insulin glargine, basal insulin, and microvascular complications. RESULTS: Large-scale intervention trials, such as the United Kingdom Prospective Diabetes Study (UKPDS), have reported that patients with type 2 DM treated with oral combination therapy are unable to maintain glycemic control. These observations have led to a reassessment of the role of insulin therapy in type 2 DM. The importance of tight glycemic control through the aggressive use of insulin early in the course of the disease is apparent from the UKPDS, Diabetes Control and Complications Trial, and other, smaller studies. Considerable evidence indicates that initiating a basal insulin-replacement strategy with an existing oral regimen can result in regaining glycemic control. Evidence emerging from recent studies indicates that use of intensive insulin therapy early in the course of the disease may have a positive clinical impact on outcome and slow the progression of complications. The availability of basal insulin analogues has expanded treatment options and improved the efficacy of therapeutic regimens for type 2 DM. CONCLUSIONS: The available data suggest using an earlier transition from monotherapy to combination therapy to minimize disease-associated morbidity. The availability of new insulin analogues has expanded therapeutic options and offers the potential to enhance the efficacy of therapeutic regimens for type 2 DM as well as improve the ease and safety of treatment when glycosylated hemoglobin cannot be maintained <7% on > or =1 oral antidiabetic agent.
Blood Glucose↗
Fine-tuning therapy with basal insulin for optimal glycemic control in type 2 diabetes: a review.
OBJECTIVE: To review results from clinical studies utilizing basal insulin therapy and discuss the impact of intensive glycemic control using forced-titration algorithms to fine-tune insulin dosing in patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: A Medline and PubMed search was undertaken for the years 1991-2004 using the following search terms: insulin, diabetes therapy, forced titration, glycemic control, and intensive insulin therapy. RESULTS: The United Kingdom Prospective Diabetes Study demonstrated that the great majority of patients with type 2 diabetes will eventually require insulin and have provided level IA evidence that intensive glycemic control improves patient outcomes. Several recently published studies in patients with type 2 diabetes showed that forced titration of basal insulin shows promise in reaching glycemic goals. Forced-titration algorithms employ a structured approach in helping patients achieve glycemic targets: doses are adjusted until glycemic goals (predefined glycosylated hemoglobin concentrations and/or blood glucose levels) are met. CONCLUSION: Studies have indicated that forced-titration regimens using insulin analogs to attain aggressive glycemic targets have the potential to improve outcomes in patients with type 2 diabetes without compromising patient safety. These forced-titration algorithms are straightforward and designed to be adaptable to individual needs, which may help overcome barriers to insulinization of patients with type 2 diabetes.
Blood Glucose↗
Insulin glulisine provides improved glycemic control in patients with type 2 diabetes.
OBJECTIVE: Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin. RESEARCH DESIGN AND METHODS: In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this randomized, multicenter, multinational, open-label, parallel-group study. Subjects were allowed to continue the same dose of prestudy regimens of oral antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose change). RESULTS: A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI (-0.46 vs. -0.30% with RHI; P = 0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs. 9.02 mmol/l]; P < 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l]; P < 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall, nocturnal, and severe) and weight gain were comparable between the two treatment groups. There were no between-group differences in baseline-to-end point changes in insulin dose. CONCLUSIONS: Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs. The clinical relevance of such a difference remains to be established.
Aged↗