Prandial glucose regulation with repaglinide: its clinical and lifestyle impact in a large cohort of patients with Type 2 diabetes

Landgraf, R.; Frank, M; Bauer, Christiane; Dieken, MarkusLeyck

doi:10.1038/sj.ijo.0801424

Cited by 43 publications

(15 citation statements)

References 28 publications

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“…We also found that repaglinide improves fasting (preprandial) glucose levels as well as HbA 1c levels despite only 4 weeks of treatment. The findings match those in other studies with repaglinide (27)(28)(29). The fact that the reduction in prandial glucose excursions induced by this short-acting compound also leads to a reduction in fasting glycemia clearly underlines the importance of controlling prandial glycemia.…”

Section: Figure 2-plasma Insulin and Blood Glucose Levels At Baselinesupporting

confidence: 80%

Optimizing Insulin Secretagogue Therapy in Patients With Type 2 Diabetes

et al. 2002

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OBJECTIVE -Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals. RESEARCH DESIGN AND METHODS -The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA 1c 7.3%, and BMI 32 kg/m 2 ). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma Cpeptide concentrations were measured at baseline and after 4 weeks of treatment.RESULTS -Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA 1c levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA 1c levels) than the same total dose of repaglinide divided into morning and evening mealtime doses.CONCLUSIONS -These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes. Diabetes Care 25:342-346, 2002T ype 2 diabetes is characterized by impaired insulin secretion, usually with concomitant impaired insulin sensitivity (1,2). Insulin secretagogue therapy is therefore a logical part of therapy of type 2 diabetes when diet and lifestyle modifications fail. Secretagogue therapy is the appropriate means to augment circulating insulin levels in patients with a moderate degree of ␤-cell dysfunction; in individuals with more advanced ␤-cell dysfunction, exogenous insulin therapy may be necessary.Sulfonylureas have been used for almost five decades as insulin secretagogues in the management of type 2 diabetes. Sulfonylureas stimulate insulin secretion and thereby reduce hyperglycemia, with few side effects. Nevertheless, the long plasma half-life and the long-lasting effect of some sulfonylureas increase the risk of hypoglycemia, especially in elderly patients and in patients with renal insufficiency (3-5). As the need to achieve nearnormoglycemia becomes recognized in the light of the findings of large prospective studies, hypoglycemia is likely to become an increasingly common feature of type 2 diabetes (6,7). In add...

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Section: Figure 2-plasma Insulin and Blood Glucose Levels At Baselinesupporting

confidence: 80%

Optimizing Insulin Secretagogue Therapy in Patients With Type 2 Diabetes

et al. 2002

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“…2). These results are concordant with those of a recently completed open-label study involving a cohort of nearly 6,000 patients with type 2 diabetes that showed no weight gain associated with flexible prandial repaglinide in patients naive to antidiabetic drug therapy or switched from alternative antidiabetic agents (20). This study also showed that patients switched from sulfonylureas reduced their daily frequency of supplementary snacks.…”

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confidence: 80%

Flexible Meal-Related Dosing With Repaglinide Facilitates Glycemic Control in Therapy-Naive Type 2 Diabetes

et al. 2001

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OBJECTIVE— This double-blind randomized placebo-controlled parallel group study assessed the efficacy and safety (with particular regard to body weight and hypoglycemia) of repaglinide when used in a flexible mealtime dosing regimen in a situation close to everyday clinical practice. RESEARCH DESIGN AND METHODS— A total of 408 patients with type 2 diabetes considered poorly controlled by diet, but without a history of previous antidiabetic medication, were randomized to receive 0.5 mg repaglinide at mealtimes (increased to 1 mg after 4 weeks depending on blood glucose response) or placebo for 16 weeks. Patients were free to choose a flexible meal pattern, adjusting the dosing schedule from two to four preprandial doses per day in accordance with a “one meal, one dose; no meal, no dose” principle. Additional snacks were not a requirement of the treatment schedule. RESULTS— Treatment with repaglinide significantly improved glycemic control with respect to baseline and placebo, reducing HbAlc by 1.14% from baseline and fasting plasma glucose by 1.8 mmol/l. Improvement in glycemic control was independent of the meal pattern adopted by patients, including those most commonly taking two or four meals daily, with no correlation between meal pattern and risk of hypoglycemia. The improvement in glycemic control was also independent of degree of obesity and age ≤65 or >65 years. There was no significant body weight increase in the repaglinide group. CONCLUSIONS— Mealtime dosing with repaglinide is effective in improving overall glycemic control in type 2 diabetic patients for which control is suboptimal using diet alone. Patients are able to vary their meal pattern from a conventional regimen of three meals daily without compromising control or increasing the risk of adverse events.

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“…In therapy-naive patients with diabetes mellitus, [83,[85][86][87] repagli-3.2 Renal Impairment/Failure nide reduced HbA1c, FPG, and PPG levels to the same extent as in controlled trials. None of these studies reported significant weight Several studies on repaglinide in patients with renal impairment gain in treated patients and the frequency of hypoglycemic epihave been published.…”

Section: Treatment-naive Patientsmentioning

confidence: 99%

“…As Ramadan is only of 4 weeks' duration, fructosamine instead of HbA1c has been used in most studies as the 2.5 Observational Studies (Efficacy vs Effectiveness) efficacy parameter. As a flexible pattern of meals and self-medication is warranted In table V [83][84][85][86][87] we have summarized the effects of repaglinide during this period, the use of a short-acting glucose-lowering drug on parameters of glucose metabolism as reported in observational such as repaglinide might offer some advantages. However, in studies.…”

Section: With Nph-insulin Vesp Plus Met Vs Biphasic 30/70 Human Insulmentioning

confidence: 99%

Defining the Role of Repaglinide in the Management of Type 2 Diabetes Mellitus

Johansen¹,

Birkeland

2007

American Journal of Cardiovascular Drugs

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Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to a combination of insulin resistance and impaired insulin secretion. The hyperglycemia is associated with an increased risk for micro- and macrovascular complications, and lowering fasting and postprandial hyperglycemia may be protective against these complications. Repaglinide is an insulin secretagogue that lowers blood glucose levels in patients with T2DM. We review the effects of repaglinide in patients with T2DM, its impact on glycemia and its non-glycemic effects, and its effects when used in special situations or patient populations. Results from randomized controlled trials, observational studies, and safety reports involving humans and published in the English-language through 1 May 2007 identified by a search in PubMed/MEDLINE were evaluated. Present knowledge indicates that repaglinide reduces fasting and postprandial hyperglycemia and the level of glycosylated hemoglobin (HbA1c) in patients with T2DM. It is at least as effective in reducing HbA1c and fasting plasma glucose as sulphonylureas, metformin, or the glitazones and in combination therapy with other drugs, repaglinide is as effective as any other combination. Some studies show a better effect of repaglinide on postprandial glycemia than the comparators. Its propensity to induce hypoglycemia is similar to or a little less than that of sulphonylureas. Repaglinide is associated with less weight gain than sulphonylureas and the glitazones. Repaglinide has primarily a role in the treatment of T2DM when metformin cannot be used due to adverse effects, when metformin fails to adequately control blood glucose levels, when there is a need for flexible dosing (i.e. the elderly or during Ramadan fasting), or when there is a specific wish to lower postprandial glucose. Repaglinide may also have an advantage when an oral agent is needed in diabetic patients with renal impairment. Because of its short duration of action, repaglinide should be taken before each meal, usually at least three times a day. Although no study has investigated whether repaglinide lowers total mortality or cardiovascular endpoints, several studies indicate beneficial effects on cardiovascular surrogate endpoints, such as carotid intima-media thickening, markers of inflammation, platelet activation, lipid parameters, endothelial function, adiponectin, and oxidative stress. In conclusion, repaglinide is a compound that can be used in both mono- and combination therapy for the treatment of both fasting and postprandial hyperglycemia in patients with T2DM. It can be used in patients at different stages of the disease, from uncomplicated to severe renal impairment. Although the drug has been tested in a large number of clinical trials and observational studies, its world-wide use is far less than, for example, sulphonylureas. Repaglinide may offer an additional potential for lowering blood glucose levels in T2DM that until now has not been fully realized by many clinicians.

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Prandial glucose regulation with repaglinide: its clinical and lifestyle impact in a large cohort of patients with Type 2 diabetes

Cited by 43 publications

References 28 publications

Optimizing Insulin Secretagogue Therapy in Patients With Type 2 Diabetes

Optimizing Insulin Secretagogue Therapy in Patients With Type 2 Diabetes

Flexible Meal-Related Dosing With Repaglinide Facilitates Glycemic Control in Therapy-Naive Type 2 Diabetes

Defining the Role of Repaglinide in the Management of Type 2 Diabetes Mellitus

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