Effects of exenatide versus insulin analogues on weight change in subjects with type 2 diabetes: a pooled post-hoc analysis

Glass, Leonard; Qu, Yongming; Lenox, Sheila M.; Kim, Dennis; Gates, Jeffrey R.; Brodows, Robert G.; Trautmann, Michael E.; Bergenstal, Richard M.

doi:10.1185/030079908x260862

Cited by 31 publications

(21 citation statements)

References 18 publications

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“…3 kg at 6 months), and this was at least 5% body weight in ~22% and at least 10% weight loss in 3.2% of patients. In contrast, most insulin-treated subjects (75.9%) had gained weight (mean 3 kg) [31]. …”

Section: Approved and Experimental Peripherally-directed Pharmacotmentioning

confidence: 99%

Peripheral mechanisms in the control of appetite and related experimental therapies in obesity

Camilleri

2009

Regulatory Peptides

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The function of the stomach and the gut hormonal responses to food ingestion constitute highly integrated homeostatic responses that maintain euglycemia and normal digestion. This intrinsic feedback involves vagal and hormonal mechanisms. Important signals such as GLP-1 and PYY that arise peripherally induce satiation and also delay gastric emptying or increase insulin secretion. Novel therapies are being developed to mimic or enhance these feedback mechanisms and to control appetite as a means to treat obesity.

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Section: Approved and Experimental Peripherally-directed Pharmacotmentioning

confidence: 99%

Peripheral mechanisms in the control of appetite and related experimental therapies in obesity

Camilleri

2009

Regulatory Peptides

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“…Furthermore, cost-effectiveness analysis also showed that exenatide is comparable to insulin glargine, glibenclamide and pioglitazone when combined with metformin. In a post hoc analysis of pooled data from two other studies, the use of exenatide was compared with insulin analogues (either insulin glargine or biphasic insulin aspart) with changes in weight as the main endpoint; the use of exenatide over 6 month period was associated with an average weight loss of 3 kg whilst patients on insulin gained weight [27]. …”

Section: Exenetide Use In the Management Of T2dm And Comparison Wimentioning

confidence: 99%

Exenatide Use in the Management of Type 2 Diabetes Mellitus

Kyriacou

Ahmed

2010

Pharmaceuticals

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Exenatide is a GLP-1 (glucagon-like peptide-1) agonist that has been approved in the UK for use in the management of Type 2 Diabetes Mellitus (T2DM) since 2006. It acts by increasing glucose-induced insulin release and by reducing glucagon secretion postprandially. It therefore increases insulin secretion and reduces glucose levels, especially postprandially. It also reduces gastric emptying and acts centrally to promote satiety. In clinical practice it reduces HbA1c (range; -0.4% to -1.3%), fasting and postprandial blood glucose levels and is the only antidiabetic agent (together with liraglutide; a human GLP-1 analogue) to promote weight loss (range; -1.5 kg to -5.5 kg). It can be used as monotherapy or in combination with metformin and/or sulphonylureas (SU) and/or thiazolinediones (TZD). When compared with insulin it causes similar reductions in HbA1c and glucose levels, but unlike insulin it has the advantage of inducing weight loss. Its main side effect is gastrointestinal (GI) disturbances; nausea is the commonest GI adverse effect, albeit usually mild and transient. Hypoglycaemia is uncommon, especially when used as monotherapy or in combination with metformin. In this review article we scrutinize the currently available evidence for use of exenatide in the management of T2DM.

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“…Glass et al48 pooled data from the above two studies,45,47 to analyze the effect of EXE vs insulins (GLA or BIASP) on weight after 6 months of treatment. Patient demographics for those receiving EXE were as follows: N = 532, mean ±SD age 59.4 ±8.8 years, 54.3% males, 87% Caucasians and 8.3% Hispanics, 9.9 ±6.1 years with DM; for those in the INS group, N = 515, 58.2 ±9.3 years, 53% males, 86.6% Caucasians and 7.8% Hispanics, with 9.6 ±6.0 years with DM.…”

Section: Clinical Efficacy and Safetymentioning

confidence: 99%

“…At endpoint, a higher number of patients in the EXE group reported a BMI < 25 kg/m 2 ( P < 0.0001 vs BL and P < 0.0001 vs INS) and a smaller number of patients reported a BMI ≥ 30 kg/m 2 ( P < 0.0001 vs BL and P > 0.0001 vs INS); more patients in the INS group reported a BMI ≥ 30 kg/m 2 vs BL ( P < 0.0001). 48…”

Section: Clinical Efficacy and Safetymentioning

confidence: 99%

A review of exenatide as adjunctive therapy in patients with type 2 diabetes

Robles¹

2009

DDDT

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BackgroundIncretin glucagon-like peptide-1 (GLP-1) is a hormone released from cells in the gastrointestinal tract (GI), leading to glucose-dependent insulin release from the pancreas. It also suppresses postprandial hyperglycemia, glucagon secretion and slows gastric emptying. Exenatide (EXE), a functional analog of human GLP-1, was approved by the US FDA in April 2005.ObjectiveThis article reviews current primary literature on the clinical efficacy and safety of EXE in the treatment of type 2 diabetes mellitus (DM) and describes the pharmacokinetics, pharmacodynamics, dosing and administration of EXE.MethodsEnglish-language articles were identified through a search of MEDLINE (1966 to March 2009), International Pharmaceutical Abstracts (1970 to present), and Cochrane Database of Systemic Reviews (1995 to March 2009). Search terms included EXE, diabetes mellitus, postprandial hyperglycemia, gastric emptying, glucagon, pharmacokinetics and pharmacodynamics. Articles were selected for review if their designs were randomized, blinded and of controlled design that focused on clinical outcomes of patients with type 2 DM.ResultsEXE is administered subcutaneously in the thigh, abdomen or upper arm within the 60-minute period before the morning and evening meals. Its Cmax is reached within 2.1 hours, and its T1/2 in 2.4 hours. EXE’s metabolism is primarily through the kidneys. For the patients who received EXE 10 μg SC BID in three, 30-week, placebo-controlled studies with background sulfonylureas (SUs), metformin (MET), or SU + MET, there were significant reductions in HbA1c (0.77 to 0.86%), fasting plasma glucose (0.6 mmol/L) and body weight (1.6 to 2.8 kg) (P ≤ 0.05 vs PCB) that were sustained in patients who completed two open-label phase trials with an additional 52 weeks of therapy. The use of thiazolidinediones was associated with a slight advantage over EXE in improving HbA1c along with increased weight gain; those who received EXE lost weight, but experienced more GI adverse effects. Patients who received EXE lost significant body weight while patients who received insulin gained weight. Patients receiving insulin had lower fasting, prelunch and predinner glucose excursions while patients in the EXE groups had lower postprandial glucose levels. Nausea was most frequently (>20%) reported in patients receiving the highest dose of EXE (10 μg SC BID vs 5 μg SC BID).ConclusionsEXE at the dose of 10 μg SC BID has been proven to decrease HbAlc by 1.3% ± 0.1% and decrease body weight by up to 5.3 ± 0.8 kg at week 82. Nausea was the most frequently reported adverse event (>20%) especially in patients being treated with EXE 10 μg SC BID. EXE can be safely added to MET therapy, SU therapy or MET + SU combination to effectively target glycemic goals in patients with type 2 DM. Long-term, head-to-head studies assessing the effect of the EXE ± oral agents/insulins in patients with HbAlc ≥ 10% are still needed to fully clarify the role of EXE in poorly controlled patients with type 2 DM.

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Effects of exenatide versus insulin analogues on weight change in subjects with type 2 diabetes: a pooled post-hoc analysis

Cited by 31 publications

References 18 publications

Peripheral mechanisms in the control of appetite and related experimental therapies in obesity

Peripheral mechanisms in the control of appetite and related experimental therapies in obesity

Exenatide Use in the Management of Type 2 Diabetes Mellitus

A review of exenatide as adjunctive therapy in patients with type 2 diabetes

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