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Milan Zdravkovic - One of the best experts on this subject based on the ideXlab platform.

  • effect of the once daily human glp 1 analogue Liraglutide on appetite energy intake energy expenditure and gastric emptying in type 2 diabetes
    Diabetes Research and Clinical Practice, 2012
    Co-Authors: Michael Horowitz, Anne Flint, M F Rasmussen, Charlotte Hindsberger, Milan Zdravkovic, Karen L Jones, Christoph Kapitza, Selena Doran, Thomas Jax, Ian Chapman
    Abstract:

    Abstract Aims Liraglutide reduces bodyweight in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanisms underlying this effect. Methods The comparative effects of Liraglutide, glimepiride and placebo on energy intake, appetite, nausea, gastric emptying, antral distension, bodyweight, gastrointestinal hormones, fasting plasma glucose and resting energy expenditure (REE), were assessed in subjects with T2DM randomised to treatment A (Liraglutide–placebo), B (placebo–glimepiride) or C (glimepiride–Liraglutide). Assessments were performed at the end of each 4-week treatment period. Results Energy intake was less (NS) with Liraglutide vs placebo and glimepiride, and 24-h REE was higher (NS) with Liraglutide vs placebo and glimepiride. Fasting hunger was less ( p  = 0.01) with Liraglutide vs placebo and glimepiride, and meal duration was shorter with Liraglutide ( p  = 0.002) vs placebo. Paracetamol AUC 0–60min and C max were less ( p p  ≤ 0.001) after Liraglutide vs placebo and glimepiride. Bodyweight reductions of 1.3 and 2.0 kg were observed with Liraglutide vs placebo and glimepiride ( p Conclusion Liraglutide caused decreased gastric emptying and increased reduction in bodyweight. The mechanisms of the Liraglutide-induced weight-loss may involve a combined effect on energy intake and energy expenditure.

  • treatment with Liraglutide a once daily glp 1 analog does not reduce the bioavailability of ethinyl estradiol levonorgestrel taken as an oral combination contraceptive drug
    The Journal of Clinical Pharmacology, 2011
    Co-Authors: Lisbeth V Jacobsen, Jan Vouis, Charlotte Hindsberger, Milan Zdravkovic
    Abstract:

    Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, Liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of Liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during Liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during Liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with Liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with Liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with Liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.

  • metabolism and excretion of the once daily human glucagon like peptide 1 analog Liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase iv and neutral endopeptidase
    Drug Metabolism and Disposition, 2010
    Co-Authors: Monika Malmerjefalt, Milan Zdravkovic, Inga Bjornsdottir, Jan Vanggaard, Hans Helleberg, Uffe Larsen, B Oosterhuis, Jan Jaap Van Lier, Annette K Olsen
    Abstract:

    Liraglutide is a novel once-daily human glucagon-like peptide (GLP)-1 analog in clinical use for the treatment of type 2 diabetes. To study metabolism and excretion of [(3)H]Liraglutide, a single subcutaneous dose of 0.75 mg/14.2 MBq was given to healthy males. The recovered radioactivity in blood, urine, and feces was measured, and metabolites were profiled. In addition, [(3)H]Liraglutide and [(3)H]GLP-1(7-37) were incubated in vitro with dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) to compare the metabolite profiles and characterize the degradation products of Liraglutide. The exposure of radioactivity in plasma (area under the concentration-time curve from 2 to 24 h) was represented by Liraglutide (≥89%) and two minor metabolites (totaling ≤11%). Similarly to GLP-1, Liraglutide was cleaved in vitro by DPP-IV in the Ala8-Glu9 position of the N terminus and degraded by NEP into several metabolites. The chromatographic retention time of DPP-IV-truncated Liraglutide correlated well with the primary human plasma metabolite [GLP-1(9-37)], and some of the NEP degradation products eluted very close to both plasma metabolites. Three minor metabolites totaling 6 and 5% of the administered radioactivity were excreted in urine and feces, respectively, but no Liraglutide was detected. In conclusion, Liraglutide is metabolized in vitro by DPP-IV and NEP in a manner similar to that of native GLP-1, although at a much slower rate. The metabolite profiles suggest that both DPP-IV and NEP are also involved in the in vivo degradation of Liraglutide. The lack of intact Liraglutide excreted in urine and feces and the low levels of metabolites in plasma indicate that Liraglutide is completely degraded within the body.

  • weight loss with Liraglutide a once daily human glucagon like peptide 1 analogue for type 2 diabetes treatment as monotherapy or added to metformin is primarily as a result of a reduction in fat tissue
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Johan Jendle, Michael A. Nauck, Kjeld Hermansen, M During, Milan Zdravkovic, Anders Frid, David R Matthews, Boyd Josef Gimnicher Strauss, Alan J Garber
    Abstract:

    Aim The effect on body composition of Liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). Methods These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < 40 kg/m2 (LEAD-2), < 45 kg/m2 (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to Liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to Liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. Results LEAD-2: fat percentage with Liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all Liraglutide/metformin arms. Except with Liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with Liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with Liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). Conclusion Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.

  • effect of renal impairment on the pharmacokinetics of the glp 1 analogue Liraglutide
    British Journal of Clinical Pharmacology, 2009
    Co-Authors: Lisbeth V Jacobsen, Charlotte Hindsberger, Richard Robson, Milan Zdravkovic
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Patients with Type 2 diabetes are likely to have or to develop renal impairment, which affects the pharmacokinetics of some antidiabetic treatments. • Whether dosing of the once-daily human glucagon-like peptide-1 analogue Liraglutide should be modified in patients with renal impairment has not previously been studied. WHAT THIS STUDY ADDS • Renal dysfunction was not found to increase the exposure of Liraglutide. • Hence, no dose adjustment is expected to be required in patients with Type 2 diabetes and renal impairment treated with Liraglutide. AIMS To investigate whether dose adjustment of the once-daily human glucagon-like peptide-1 analogue Liraglutide is required in patients with varying stages of renal impairment. METHODS A cohort of 30 subjects, of whom 24 had varying degrees of renal impairment and six had normal renal function, were given a single dose of Liraglutide, 0.75 mg subcutaneously, and completed serial blood sampling for plasma Liraglutide measurements for pharmacokinetic estimation. RESULTS No clear trend for change in pharmacokinetics was evident across groups with increasing renal dysfunction. While the between-group comparisons of the area under the Liraglutide concentration–curve (AUC) did not demonstrate equivalence [estimated ratio AUCsevere/AUChealthy 0.73, 90% confidence interval (CI) 0.57, 0.94; and AUC (continuous ambulatory peritoneal dialysis)CAPD/AUChealthy 0.74, 90% CI 0.56, 0.97], the regression analysis of log(AUC) for subjects with normal renal function and mild-to-severe renal impairment showed no significant effect of decreasing creatinine clearance on the pharmacokinetics of Liraglutide. The expected AUC ratio between the two subjects with the lowest and highest creatinine clearance in the study was estimated to be 0.88 (95% CI 0.58, 1.34) (NS). Degree of renal impairment did not appear to be associated with an increased risk of adverse events. CONCLUSIONS This study indicated no safety concerns regarding use of Liraglutide in patients with renal impairment. Renal dysfunction was not found to increase exposure of Liraglutide, and patients with Type 2 diabetes and renal impairment should use standard treatment regimens of Liraglutide. There is, however, currently limited experience with Liraglutide in patients beyond mild-stage renal disease.

O Santiago - One of the best experts on this subject based on the ideXlab platform.

  • effects of Liraglutide nn2211 a long acting glp 1 analogue on glycaemic control and bodyweight in subjects with type 2 diabetes
    Diabetic Medicine, 2005
    Co-Authors: Mark N Feinglos, M F Saad, F X Pisunyer, O Santiago
    Abstract:

    Aims  Liraglutide (NN2211) is a long-acting GLP-1 analogue, with a pharmacokinetic profile suitable for once-daily administration. This multicentre, double-blind, parallel-group, double-dummy study explored the dose–response relationship of Liraglutide effects on bodyweight and glycaemic control in subjects with Type 2 diabetes. Methods  Subjects (BMI 27–42 kg/m2) with Type 2 diabetes who were previously treated with an OAD (oral anti-diabetic drug) monotherapy (69% with metformin), and had HbA1c ≤ 10% were enrolled. After a 4-week metformin run-in period, 210 subjects (27–73 years, 60% female) were randomised to receive Liraglutide (0.045–0.75 mg) once daily or continued on metformin 1000 mg b.d. for 12 weeks. Results  Mean baseline values for the six treatment groups ranged from 6.8 to 7.5% for HbA1c, and 8.06–9.44 mmol/l (145–170 mg/dl) for fasting plasma glucose. After 12-week treatment, a weight change of −0.05 to −1.9% was observed for the six treatment groups. Mean HbA1c changes from baseline for 0.045, 0.225, 0.45, 0.6, 0.75 mg Liraglutide and metformin were +1.28%, +0.86%, +0.22%, +0.16%, +0.30% and +0.09%, respectively. No significant differences in HbA1c were observed between Liraglutide and metformin groups at the three highest Liraglutide dose levels (0.45, 0.6 and 0.75 mg). The lowest two Liraglutide doses (0.045 mg and 0.225 mg) were not sufficient to maintain the fasting plasma glucose values achieved by metformin. No major hypoglycaemic episodes were reported. Episodes of nausea and/or vomiting were reported by 11 patients (6.3%) receiving Liraglutide and three (8.8%) receiving metformin. Conclusions  Once-daily Liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of Liraglutide merit study in future clinical trials.

T. Imaoka - One of the best experts on this subject based on the ideXlab platform.

  • once weekly glucagon like peptide 1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once daily Liraglutide in japanese patients with type 2 diabetes 52 weeks of treatment in a randomized phase iii study
    Diabetes Obesity and Metabolism, 2016
    Co-Authors: Masato Odawara, J. Miyagawa, N. Iwamoto, Yasushi Takita, T. Imaoka, Toshinari Takamura
    Abstract:

    Aims To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily Liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks. Methods We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; Liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for Liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with Liraglutide for 52 weeks. Results At week 52, dulaglutide decreased HbA1c significantly from baseline compared with Liraglutide [least squares mean difference: −0.20; 95% confidence interval (CI) −0.39, −0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose (BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with Liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four Liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe. Conclusions Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily Liraglutide 0.9 mg.

  • once weekly glucagon like peptide 1 receptor agonist dulaglutide is non inferior to once daily Liraglutide and superior to placebo in japanese patients with type 2 diabetes a 26 week randomized phase iii study
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: J. Miyagawa, Masato Odawara, Toshinari Takamura, N. Iwamoto, Yasushi Takita, T. Imaoka
    Abstract:

    Aims To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily Liraglutide (0.9 mg) in Japanese patients with type 2 diabetes. Methods This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (Liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; Liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for Liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26 weeks. Analyses were performed on the full analysis set. Results At 26 weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily Liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo −1.57% (95% confidence interval −1.79 to −1.35); dulaglutide vs Liraglutide −0.10% (95% confidence interval −0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and Liraglutide groups [dulaglutide, n = 2 (0.7%); Liraglutide, n = 8 (5.8%); p = 0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n = 6 (2.1%); Liraglutide, n = 2 (1.5%); placebo, n = 1 (1.4%)], with no event being severe. Conclusions In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75 mg) was superior to placebo and non-inferior to once-daily Liraglutide (0.9 mg) for reduction in HbA1c at 26 weeks. Dulaglutide was safe and well tolerated.

Toshinari Takamura - One of the best experts on this subject based on the ideXlab platform.

  • once weekly glucagon like peptide 1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once daily Liraglutide in japanese patients with type 2 diabetes 52 weeks of treatment in a randomized phase iii study
    Diabetes Obesity and Metabolism, 2016
    Co-Authors: Masato Odawara, J. Miyagawa, N. Iwamoto, Yasushi Takita, T. Imaoka, Toshinari Takamura
    Abstract:

    Aims To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily Liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks. Methods We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; Liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for Liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with Liraglutide for 52 weeks. Results At week 52, dulaglutide decreased HbA1c significantly from baseline compared with Liraglutide [least squares mean difference: −0.20; 95% confidence interval (CI) −0.39, −0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose (BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with Liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four Liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe. Conclusions Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily Liraglutide 0.9 mg.

  • once weekly glucagon like peptide 1 receptor agonist dulaglutide is non inferior to once daily Liraglutide and superior to placebo in japanese patients with type 2 diabetes a 26 week randomized phase iii study
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: J. Miyagawa, Masato Odawara, Toshinari Takamura, N. Iwamoto, Yasushi Takita, T. Imaoka
    Abstract:

    Aims To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily Liraglutide (0.9 mg) in Japanese patients with type 2 diabetes. Methods This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (Liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; Liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for Liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26 weeks. Analyses were performed on the full analysis set. Results At 26 weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily Liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo −1.57% (95% confidence interval −1.79 to −1.35); dulaglutide vs Liraglutide −0.10% (95% confidence interval −0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and Liraglutide groups [dulaglutide, n = 2 (0.7%); Liraglutide, n = 8 (5.8%); p = 0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n = 6 (2.1%); Liraglutide, n = 2 (1.5%); placebo, n = 1 (1.4%)], with no event being severe. Conclusions In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75 mg) was superior to placebo and non-inferior to once-daily Liraglutide (0.9 mg) for reduction in HbA1c at 26 weeks. Dulaglutide was safe and well tolerated.

Alan M Garber - One of the best experts on this subject based on the ideXlab platform.

  • one year of Liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin both in combination with metformin in patients with type 2 diabetes a randomised parallel group open label trial
    International Journal of Clinical Practice, 2011
    Co-Authors: Richard E Pratley, Alan M Garber, Michael A. Nauck, Timothy L Bailey, Eduard Montanya, Robert Cuddihy, Sebastiano Filetti, A B Thomsen, H Hartvig, Melanie J Davies
    Abstract:

    Summary Aim:  The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue Liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes. Methods:  In an open-label, parallel-group trial, metformin-treated participants were randomised to Liraglutide 1.2 mg/day (n = 225), Liraglutide 1.8 mg/day (n = 221) or sitagliptin 100 mg/day (n = 219) for 26 weeks (main phase). Participants continued the same treatment in a 26-week extension. Results:  Liraglutide (1.2 or 1.8 mg) was superior to sitagliptin for reducing HbA1c from baseline (8.4–8.5%) to 52 weeks: −1.29% and −1.51% vs. −0.88% respectively. Estimated mean treatment differences between Liraglutide and sitagliptin were as follows: −0.40% (95% confidence interval −0.59 to −0.22) for 1.2 mg and −0.63% (−0.81 to −0.44) for 1.8 mg (both p < 0.0001). Weight loss was greater with Liraglutide 1.2 mg (−2.78 kg) and 1.8 mg (−3.68 kg) than sitagliptin (−1.16 kg) (both p < 0.0001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly more with Liraglutide 1.8 mg than with sitagliptin (p = 0.03). Proportions of participants reporting adverse events were generally comparable; minor hypoglycaemia was 8.1%, 8.3% and 6.4% for Liraglutide 1.2 mg, 1.8 mg and sitagliptin respectively. Gastrointestinal side effects, mainly nausea, initially occurred more frequently with Liraglutide, but declined after several weeks. Conclusion:  Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks. Treatment satisfaction was significantly greater with 1.8 mg Liraglutide, similar to 26-week results. The safety profiles of Liraglutide and sitagliptin are consistent with previous reports.

  • Liraglutide a once daily human glucagon like peptide 1 analogue provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes
    Diabetes Obesity and Metabolism, 2011
    Co-Authors: Alan M Garber, Paula M Hale, Robert R Henry, Robert E Ratner, C T Chang, Bruce W Bode
    Abstract:

    Aims: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of Liraglutide monotherapy compared with glimepiride monotherapy over 2 years. Methods: Participants were randomized to receive once-daily Liraglutide 1.2 mg, Liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. Results: For patients completing 2 years of therapy, HbA1c reductions were −0.6% with glimepiride versus −0.9% with Liraglutide 1.2 mg (difference: −0.37, 95% CI: −0.71 to −0.02; p = 0.0376) and −1.1% with Liraglutide 1.8 mg (difference: −0.55, 95% CI: −0.88 to −0.21; p = 0.0016). In the ITT population, HbA1c reductions were −0.3% with glimepiride versus −0.6% with Liraglutide 1.2 mg (difference: −0.31, 95% CI: −0.54 to −0.08; p = 0.0076) and −0.9% with Liraglutide 1.8 mg (difference: −0.60, 95% CI: −0.83 to −0.38; p < 0.0001). For both ITT and completer populations, Liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with Liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). Conclusion: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.

  • Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events results from the Liraglutide effect and action in diabetes lead trials
    The Journal of Clinical Endocrinology and Metabolism, 2011
    Co-Authors: John B Buse, Alan M Garber, W E Schmidt, Julio Rosenstock, Jason Brett, Nicoline Videbaek, Jens J Holst, Michael A. Nauck
    Abstract:

    Anti-Liraglutide antibody formation was infrequent; antibody levels were low and did not decrease the glycemic response to Liraglutide; Liraglutide was less immunogenic than exenatide.

  • patient reported outcomes following treatment with the human glp 1 analogue Liraglutide or glimepiride in monotherapy results from a randomized controlled trial in patients with type 2 diabetes
    Diabetes Obesity and Metabolism, 2010
    Co-Authors: Bruce W Bode, Mette Hammer, M Testa, M Magwire, Paula M Hale, Lawrence Blonde, Alan M Garber
    Abstract:

    Aim: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether Liraglutide treatment could improve these factors. Methods: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with Liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). Results: Mean (SE) decreases in glycated haemoglobin levels were greater with Liraglutide 1.2 mg [−0.84 (0.08)%] and 1.8 mg [−1.14 (0.08)%] than glimepiride [−0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on Liraglutide [1.2 mg: −2.05 (0.28) kg; 1.8 mg: −2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with Liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and Liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331–0.696]. Mean (SE) weight concerns were less with Liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with Liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41–0.73). Mean (SE) mental and emotional health and general perceived health improved more with Liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. Conclusions: Improved glycaemic control and decreased weight with Liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain.