Incretin-Based Therapies and Cardiovascular Disease
Incretin-Based Therapies and Cardiovascular Disease
A majority of patients with type 2 diabetes are overweight or obese which contributes to their CVD risk. When managing diabetes, it is important to consider that some antihyperglycaemic agents cause weight gain, while others have shown neutral effects on weight or beneficial effects on weight loss. The proposed mechanism of DPP-4 inhibitors on body weight is derived from the understanding of how gut-derived incretin hormones act, specifically GLP-1, by decreasing appetite and increasing satiety. DPP-4 inhibitors inhibit the breakdown of GLP, prolonging its physiological effects. Evaluation of the effect of DPP-4 inhibitors on body weight is limited to secondary end-points from RCTs, which are summarised in Table S1 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0001-TableS1.xlsb?v=1&s=3a7932dad651c9a184537023417da3cdf43d8816. Alogliptin monotherapy has shown non-significant decreases in body weight compared with placebo. However, when alogliptin is combined with other antihyperglycaemic agents as add-on therapy, the effects on body weight appear to favour the effects of the other agents. For example, when added to pioglitazone, glyburide and insulin, non-significant increases in body weight occurred, whereas when added to metformin and viglibose (an alpha-glucosidase inhibitor), non-significant decreases occurred. For linagliptin, similar non-significant effects were observed when combined with other antihyperglycaemic agents. When linagliptin was compared with glimepiride as add-on therapy with metformin, there was a significant mean treatment difference of −2.7 kg in favour of linagliptin. Saxagliptin monotherapy has shown non-significant decreases in body weight when compared with placebo. Saxagliptin added to metformin provides additional numerical decreases in body weight all of which are non-significant. When saxagliptin was compared with glipizide as add-on therapy with metformin, there was a significant between-group difference of −2.2 kg at 52 weeks of therapy which was sustained at 104 weeks. When saxagliptin was added to insulin and a TZD, non-significant increases in body weight were described.
Of the DPP-4 inhibitors, sitagliptin has the largest amount of literature comparing multiple regimens. When sitagliptin was compared with placebo, a significant change from baseline was noted only for placebo (−1.1 kg ± 0.2; p < 0.01) and not sitagliptin (−0.2 kg ± 0.2). When sitagliptin was compared with metformin, a significant between-group difference was noted in favour of metformin. Adding sitagliptin to metformin therapy provided additional reductions from baseline. Non-significant decreases were observed for the following regimens: sitagliptin as add-on therapy to metformin plus insulin detemir, sitagliptin as add-on therapy to metformin plus an SU, sitagliptin compared with placebo, and sitagliptin as add-on therapy to metformin. As observed with other DPP-4 inhibitors, when compared with glimepiride, glibenclamide (known as glyburide in the United States), glipizide, pioglitazone, rosiglitazone and insulin glargine, significant between-group differences or mean changes from baseline were observed all favouring sitagliptin therapy.
Vildagliptin also has a large amount of literature comparing multiple regimens. When vildagliptin was compared with placebo as monotherapy and as add-on therapy to metformin, there were significant decreases only in placebo arms (−1.4 kg ± 0.4; p < 0.001) and (−1.0 kg ± 0.3; p < 0.001), respectively. In the vildagliptin arms of these studies, the results were mixed with significant (−0.18 kg ± 0.4; p < 0.001) and non-significant decreases from baseline. When vildagliptin was compared directly to metformin, there was a significant decrease in body weight for metformin (−1.9 kg ± 0.3; p < 0.001). Vildagliptin has been studied primarily with TZDs or SUs, either in combination with or compared with an agent from one of these drug classes as add-on therapy. When vildagliptin was compared as add-on therapy to metformin vs. pioglitazone and glimepiride, there were significant between-group differences (−1.6 kg ± 0.3; p < 0.001) (−1.79 kg ± 0.16; p < 0.001), and (−1.5 kg ± 0.2; p < 0.001) in favour of vildagliptin therapy. At various dosages of vildagliptin added to pioglitazone, non-significant increases in body weight were observed. Similar results occurred when vildagliptin was added to rosiglitazone.
Overall, the effects DPP-4 inhibitors have on body weight appear to be neutral. Typically, when any of the DPP-4 inhibitors are added to agents known to cause weight gain (i.e. insulin, SUs, or TZDs) increases in body weight are observed. Similarly, when DPP-4 inhibitors are added to agents known to cause weight loss (i.e. metformin or alpha-glucosidase inhibitors), decreases in body weight are observed. These results support the argument that DPP-4 inhibitors have little effect on body weight and will not induce added weight gain or weight loss.
Glucagon-like peptide 1 receptor agonists are resistant to DPP-4 degradation and their concentrations are supra-physiological, which significantly prolongs and enhances the activity of GLP-1. For GLP-1 receptor agonists, the evidence indicates that these agents have more substantial effects on body weight compared with DPP-4 inhibitors. RCTs evaluating the effect of GLP-1 receptor agonists on body weight as a secondary endpoint are summarised in Table S2 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0002-TableS2.xlsb?v=1&s=5ba1bad889711dc9ce3dddf1d124671aea3f46de.
Weight loss with exenatide, the first GLP-1 receptor agonist introduced to the market, was demonstrated in animal models and early clinical trials. When exenatide 10 μg twice daily (bid) was compared with placebo in newly diagnosed patients with type 2 diabetes, a mean end-of-study 3.1-kg weight loss was observed with exenatide compared with a 1.4-kg weight gain with placebo (p < 0.001). When exenatide 5 and 10 μg bid were added to pre-existing SU therapy, the investigators observed a progressive weight loss throughout the 30-week study period and a mean end-of-study weight loss of 1.6 kg with exenatide 10 μg, which was statistically significant from the 0.6 kg weight loss observed in the placebo group (p < 0.05). There was a mean end-of-study weight loss of 0.9 kg with exenatide 5 μg, which was not statistically significant compared with placebo.
Weight loss effects were greater when exenatide was added to pre-existing metformin therapy. A progressive weight loss over the 30-week study period and a mean end-of-study 2.8-kg weight loss were observed with exenatide 10 μg bid compared with a 0.3-kg weight loss with placebo (p ≤ 0.001). A statistically significant, but smaller mean weight loss of 1.6 kg was observed with exenatide 5 μg bid compared with placebo (p ≤ 0.05). Weight loss occurred in patients regardless of baseline body mass index (BMI). Similar results were observed in a small study of 69 patients. There was a mean 3.9-kg weight loss in patients taking metformin in combination with exenatide for a year compared with a 0.3-kg weight loss in patients taking metformin in combination with insulin glargine (p = 0.01).
In another study, a mean weight loss of 1.6 kg was observed when exenatide 5 μg bid or 10 μg bid was added to a pre-existing regimen of metformin and an SU. This observed weight loss was greater than the 0.9-kg mean end-of-study weight loss observed in the placebo group (p ≤ 0.01). Similarly, a 1.51-kg mean end-of-study weight loss was observed when exenatide 10 μg bid was added to pre-existing TZD monotherapy (21% of participants) or the combination of TZD and metformin (79% of participants) compared with a 0.21-kg weight loss observed in the placebo arm (p < 0.001).
An extended duration study of 82 weeks in total, showed weight loss to continue beyond the 30-week study periods of previously conducted RCTs. Patients were recruited from three previous studies described earlier in this section of the review into an open-label, 52-week extension trial. All patients were placed on exenatide 10 μg bid for the extension phase of the investigation. The intention-to-treat analysis showed that patients lost a mean 3.5-kg during the extension period, in addition to the mean 1.6-kg weight loss observed in the 30-week placebo-controlled phases of these studies. A correlation in baseline BMI and the degree of weight loss was observed. Patients with a baseline BMI < 25 kg/m had a mean 2-kg weight loss (2.9% loss from mean baseline weight) vs. a mean 7-kg weight loss (5.5% loss from mean baseline weight) in patients with a BMI ≥ 40 kg/m. Similar to the results of the placebo-controlled studies, this extension study showed weight loss to be greatest in those patients taking exenatide added to metformin.
Weight loss has also been observed when exenatide was added to a pre-existing regimen of insulin glargine with or without metformin and/or pioglitazone. Most patients received insulin glargine (mean dose at start of study was 49 units; 0.5 units/kg/day) in combination with metformin (~70% of study population) and the remaining patients received insulin glargine monotherapy (~15% of study population), insulin glargine in combination with metformin and pioglitazone (12% of population), or insulin glargine in combination with pioglitazone (~3% of population). A 1.8-kg mean end-of-study weight loss was observed with exenatide compared with a 1-kg weight gain with placebo (p < 0.001). On average, insulin dose titrations were smaller with exenatide compared with placebo, a 13-unit increase vs. a 20-unit increase at the end of 30 weeks, respectively (p = 0.03). This may have also accounted for some of the observed differences in weight changes. In addition, the greater weight loss with exenatide was observed although a greater percentage of exenatide-treated patients were taking pioglitazone; however, the weight gain effects of pioglitazone may have been offset by the large percentage of patients also on combination therapy with metformin.
In summary, patients who took exenatide in combination with metformin lost, on average, 3 kg compared with 1.5–1.8 kg in patients who took exenatide in combination with a SU, TZD, metformin plus SU, metformin plus TZD, insulin glargine or insulin glargine plus metformin. Moreover, when considering weight loss when exenatide is added to insulin glargine, the reader must keep in mind that the observed weight loss may have been due in part to the smaller insulin dose titrations needed with exenatide.
The exenatide extended-release (ER) formulation has produced similar weight loss observed with exenatide bid. When exenatide bid was compared with exenatide ER a similar mean end-of-study weight loss was observed, 3.6 kg vs. 3.7 kg, respectively (95% CI: −1.1 to 1.3 kg; p = 0.89) In a 22-week extension of this trial, patients who received exenatide bid during the first 30 weeks were switched to exenatide ER for the duration of the study, and those patients who were taking exenatide ER were continued on that regimen. Weight losses were similar at the end of the 52 weeks with a mean end-of-study weight loss of 4.1 kg with exenatide ER for the entire 52 weeks and 4.5 kg with exenatide bid switched to exenatide ER. When exenatide ER was added to pre-existing metformin, a mean end-of-study 2.3 kg weight loss was observed which was similar to the 2.8 kg mean end-of-study weight loss observed when exenatide bid was added to pre-existing metformin therapy.
Liraglutide has been shown to have weight loss effects similar to exenatide. A 3.24-kg mean, end-of-study weight loss was observed with liraglutide compared with a 2.87-kg weight loss with exenatide (−0.38 kg difference; 95% CI: −0.99 to 0.23; p = 0.2235). Similar weight loss has been observed with other studies of liraglutide which are summarised in Table S2 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0002-TableS2.xlsb?v=1&s=5ba1bad889711dc9ce3dddf1d124671aea3f46de. As with exenatide and SU combination therapy, less weight loss is observed when liraglutide is combined with an SU, as evidenced by the negligible 0.2-kg weight loss observed. When liraglutide was compared with albiglutide, a new GLP-1 receptor agonist recently approved by the Food and Drug Administration (FDA), weight loss was significantly greater with liraglutide, −2.19 kg vs. −0.64 kg (−1.55 kg difference; 95% CI: −2.06 to −1.05; p < 0.0001).
Dulaglutide is another GLP-1 receptor agonist recently approved by the FDA that has shown similar weight loss effects as exenatide and liraglutide. When compared with sitagliptin as add-on therapy to metformin, significant decreases from baseline were observed for dulaglutide 1.5 mg once weekly (−3.03 kg ± 0.22) and dulaglutide 0.75 mg once weekly (−2.60 kg ± 0.23) compared with placebo (p < 0.001 for both) and sitagliptin (p < 0.001 for both). When directly compared with metformin, similar weight loss was observed with dulaglutide 1.5 mg (−2.29 kg ± 0.24) and metformin (−2.22 kg ± 0.24), and significantly less weight loss was observed with dulaglutide 0.75 mg (−1.36 kg ± 0.24) compared with metformin (p = 0.003). In addition, when dulaglutide 1.5 mg once weekly was compared with liraglutide, significant decreases in weight from baseline were observed for both (−2.90 kg; p < 0.0001) and (−3.61 kg; p < 0.001), respectively.
In summary, weight loss observed among GLP-1 receptor agonists has been similar, on average ranging from 1.5 to 3 kg, with the exception of albiglutide which has shown less weight loss. This weight loss is attenuated when GLP-1 receptor agonists are combined with glucose-lowering agents known to cause weight gain (i.e. TZDs and SUs).
Effects of Incretin-based Therapies on Body Weight
DPP-4 inhibitors
A majority of patients with type 2 diabetes are overweight or obese which contributes to their CVD risk. When managing diabetes, it is important to consider that some antihyperglycaemic agents cause weight gain, while others have shown neutral effects on weight or beneficial effects on weight loss. The proposed mechanism of DPP-4 inhibitors on body weight is derived from the understanding of how gut-derived incretin hormones act, specifically GLP-1, by decreasing appetite and increasing satiety. DPP-4 inhibitors inhibit the breakdown of GLP, prolonging its physiological effects. Evaluation of the effect of DPP-4 inhibitors on body weight is limited to secondary end-points from RCTs, which are summarised in Table S1 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0001-TableS1.xlsb?v=1&s=3a7932dad651c9a184537023417da3cdf43d8816. Alogliptin monotherapy has shown non-significant decreases in body weight compared with placebo. However, when alogliptin is combined with other antihyperglycaemic agents as add-on therapy, the effects on body weight appear to favour the effects of the other agents. For example, when added to pioglitazone, glyburide and insulin, non-significant increases in body weight occurred, whereas when added to metformin and viglibose (an alpha-glucosidase inhibitor), non-significant decreases occurred. For linagliptin, similar non-significant effects were observed when combined with other antihyperglycaemic agents. When linagliptin was compared with glimepiride as add-on therapy with metformin, there was a significant mean treatment difference of −2.7 kg in favour of linagliptin. Saxagliptin monotherapy has shown non-significant decreases in body weight when compared with placebo. Saxagliptin added to metformin provides additional numerical decreases in body weight all of which are non-significant. When saxagliptin was compared with glipizide as add-on therapy with metformin, there was a significant between-group difference of −2.2 kg at 52 weeks of therapy which was sustained at 104 weeks. When saxagliptin was added to insulin and a TZD, non-significant increases in body weight were described.
Of the DPP-4 inhibitors, sitagliptin has the largest amount of literature comparing multiple regimens. When sitagliptin was compared with placebo, a significant change from baseline was noted only for placebo (−1.1 kg ± 0.2; p < 0.01) and not sitagliptin (−0.2 kg ± 0.2). When sitagliptin was compared with metformin, a significant between-group difference was noted in favour of metformin. Adding sitagliptin to metformin therapy provided additional reductions from baseline. Non-significant decreases were observed for the following regimens: sitagliptin as add-on therapy to metformin plus insulin detemir, sitagliptin as add-on therapy to metformin plus an SU, sitagliptin compared with placebo, and sitagliptin as add-on therapy to metformin. As observed with other DPP-4 inhibitors, when compared with glimepiride, glibenclamide (known as glyburide in the United States), glipizide, pioglitazone, rosiglitazone and insulin glargine, significant between-group differences or mean changes from baseline were observed all favouring sitagliptin therapy.
Vildagliptin also has a large amount of literature comparing multiple regimens. When vildagliptin was compared with placebo as monotherapy and as add-on therapy to metformin, there were significant decreases only in placebo arms (−1.4 kg ± 0.4; p < 0.001) and (−1.0 kg ± 0.3; p < 0.001), respectively. In the vildagliptin arms of these studies, the results were mixed with significant (−0.18 kg ± 0.4; p < 0.001) and non-significant decreases from baseline. When vildagliptin was compared directly to metformin, there was a significant decrease in body weight for metformin (−1.9 kg ± 0.3; p < 0.001). Vildagliptin has been studied primarily with TZDs or SUs, either in combination with or compared with an agent from one of these drug classes as add-on therapy. When vildagliptin was compared as add-on therapy to metformin vs. pioglitazone and glimepiride, there were significant between-group differences (−1.6 kg ± 0.3; p < 0.001) (−1.79 kg ± 0.16; p < 0.001), and (−1.5 kg ± 0.2; p < 0.001) in favour of vildagliptin therapy. At various dosages of vildagliptin added to pioglitazone, non-significant increases in body weight were observed. Similar results occurred when vildagliptin was added to rosiglitazone.
Overall, the effects DPP-4 inhibitors have on body weight appear to be neutral. Typically, when any of the DPP-4 inhibitors are added to agents known to cause weight gain (i.e. insulin, SUs, or TZDs) increases in body weight are observed. Similarly, when DPP-4 inhibitors are added to agents known to cause weight loss (i.e. metformin or alpha-glucosidase inhibitors), decreases in body weight are observed. These results support the argument that DPP-4 inhibitors have little effect on body weight and will not induce added weight gain or weight loss.
GLP-1 Receptor Agonists
Glucagon-like peptide 1 receptor agonists are resistant to DPP-4 degradation and their concentrations are supra-physiological, which significantly prolongs and enhances the activity of GLP-1. For GLP-1 receptor agonists, the evidence indicates that these agents have more substantial effects on body weight compared with DPP-4 inhibitors. RCTs evaluating the effect of GLP-1 receptor agonists on body weight as a secondary endpoint are summarised in Table S2 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0002-TableS2.xlsb?v=1&s=5ba1bad889711dc9ce3dddf1d124671aea3f46de.
Weight loss with exenatide, the first GLP-1 receptor agonist introduced to the market, was demonstrated in animal models and early clinical trials. When exenatide 10 μg twice daily (bid) was compared with placebo in newly diagnosed patients with type 2 diabetes, a mean end-of-study 3.1-kg weight loss was observed with exenatide compared with a 1.4-kg weight gain with placebo (p < 0.001). When exenatide 5 and 10 μg bid were added to pre-existing SU therapy, the investigators observed a progressive weight loss throughout the 30-week study period and a mean end-of-study weight loss of 1.6 kg with exenatide 10 μg, which was statistically significant from the 0.6 kg weight loss observed in the placebo group (p < 0.05). There was a mean end-of-study weight loss of 0.9 kg with exenatide 5 μg, which was not statistically significant compared with placebo.
Weight loss effects were greater when exenatide was added to pre-existing metformin therapy. A progressive weight loss over the 30-week study period and a mean end-of-study 2.8-kg weight loss were observed with exenatide 10 μg bid compared with a 0.3-kg weight loss with placebo (p ≤ 0.001). A statistically significant, but smaller mean weight loss of 1.6 kg was observed with exenatide 5 μg bid compared with placebo (p ≤ 0.05). Weight loss occurred in patients regardless of baseline body mass index (BMI). Similar results were observed in a small study of 69 patients. There was a mean 3.9-kg weight loss in patients taking metformin in combination with exenatide for a year compared with a 0.3-kg weight loss in patients taking metformin in combination with insulin glargine (p = 0.01).
In another study, a mean weight loss of 1.6 kg was observed when exenatide 5 μg bid or 10 μg bid was added to a pre-existing regimen of metformin and an SU. This observed weight loss was greater than the 0.9-kg mean end-of-study weight loss observed in the placebo group (p ≤ 0.01). Similarly, a 1.51-kg mean end-of-study weight loss was observed when exenatide 10 μg bid was added to pre-existing TZD monotherapy (21% of participants) or the combination of TZD and metformin (79% of participants) compared with a 0.21-kg weight loss observed in the placebo arm (p < 0.001).
An extended duration study of 82 weeks in total, showed weight loss to continue beyond the 30-week study periods of previously conducted RCTs. Patients were recruited from three previous studies described earlier in this section of the review into an open-label, 52-week extension trial. All patients were placed on exenatide 10 μg bid for the extension phase of the investigation. The intention-to-treat analysis showed that patients lost a mean 3.5-kg during the extension period, in addition to the mean 1.6-kg weight loss observed in the 30-week placebo-controlled phases of these studies. A correlation in baseline BMI and the degree of weight loss was observed. Patients with a baseline BMI < 25 kg/m had a mean 2-kg weight loss (2.9% loss from mean baseline weight) vs. a mean 7-kg weight loss (5.5% loss from mean baseline weight) in patients with a BMI ≥ 40 kg/m. Similar to the results of the placebo-controlled studies, this extension study showed weight loss to be greatest in those patients taking exenatide added to metformin.
Weight loss has also been observed when exenatide was added to a pre-existing regimen of insulin glargine with or without metformin and/or pioglitazone. Most patients received insulin glargine (mean dose at start of study was 49 units; 0.5 units/kg/day) in combination with metformin (~70% of study population) and the remaining patients received insulin glargine monotherapy (~15% of study population), insulin glargine in combination with metformin and pioglitazone (12% of population), or insulin glargine in combination with pioglitazone (~3% of population). A 1.8-kg mean end-of-study weight loss was observed with exenatide compared with a 1-kg weight gain with placebo (p < 0.001). On average, insulin dose titrations were smaller with exenatide compared with placebo, a 13-unit increase vs. a 20-unit increase at the end of 30 weeks, respectively (p = 0.03). This may have also accounted for some of the observed differences in weight changes. In addition, the greater weight loss with exenatide was observed although a greater percentage of exenatide-treated patients were taking pioglitazone; however, the weight gain effects of pioglitazone may have been offset by the large percentage of patients also on combination therapy with metformin.
In summary, patients who took exenatide in combination with metformin lost, on average, 3 kg compared with 1.5–1.8 kg in patients who took exenatide in combination with a SU, TZD, metformin plus SU, metformin plus TZD, insulin glargine or insulin glargine plus metformin. Moreover, when considering weight loss when exenatide is added to insulin glargine, the reader must keep in mind that the observed weight loss may have been due in part to the smaller insulin dose titrations needed with exenatide.
The exenatide extended-release (ER) formulation has produced similar weight loss observed with exenatide bid. When exenatide bid was compared with exenatide ER a similar mean end-of-study weight loss was observed, 3.6 kg vs. 3.7 kg, respectively (95% CI: −1.1 to 1.3 kg; p = 0.89) In a 22-week extension of this trial, patients who received exenatide bid during the first 30 weeks were switched to exenatide ER for the duration of the study, and those patients who were taking exenatide ER were continued on that regimen. Weight losses were similar at the end of the 52 weeks with a mean end-of-study weight loss of 4.1 kg with exenatide ER for the entire 52 weeks and 4.5 kg with exenatide bid switched to exenatide ER. When exenatide ER was added to pre-existing metformin, a mean end-of-study 2.3 kg weight loss was observed which was similar to the 2.8 kg mean end-of-study weight loss observed when exenatide bid was added to pre-existing metformin therapy.
Liraglutide has been shown to have weight loss effects similar to exenatide. A 3.24-kg mean, end-of-study weight loss was observed with liraglutide compared with a 2.87-kg weight loss with exenatide (−0.38 kg difference; 95% CI: −0.99 to 0.23; p = 0.2235). Similar weight loss has been observed with other studies of liraglutide which are summarised in Table S2 http://onlinelibrary.wiley.com/store/10.1111/ijcp.12572/asset/supinfo/IJCP12572-sup-0002-TableS2.xlsb?v=1&s=5ba1bad889711dc9ce3dddf1d124671aea3f46de. As with exenatide and SU combination therapy, less weight loss is observed when liraglutide is combined with an SU, as evidenced by the negligible 0.2-kg weight loss observed. When liraglutide was compared with albiglutide, a new GLP-1 receptor agonist recently approved by the Food and Drug Administration (FDA), weight loss was significantly greater with liraglutide, −2.19 kg vs. −0.64 kg (−1.55 kg difference; 95% CI: −2.06 to −1.05; p < 0.0001).
Dulaglutide is another GLP-1 receptor agonist recently approved by the FDA that has shown similar weight loss effects as exenatide and liraglutide. When compared with sitagliptin as add-on therapy to metformin, significant decreases from baseline were observed for dulaglutide 1.5 mg once weekly (−3.03 kg ± 0.22) and dulaglutide 0.75 mg once weekly (−2.60 kg ± 0.23) compared with placebo (p < 0.001 for both) and sitagliptin (p < 0.001 for both). When directly compared with metformin, similar weight loss was observed with dulaglutide 1.5 mg (−2.29 kg ± 0.24) and metformin (−2.22 kg ± 0.24), and significantly less weight loss was observed with dulaglutide 0.75 mg (−1.36 kg ± 0.24) compared with metformin (p = 0.003). In addition, when dulaglutide 1.5 mg once weekly was compared with liraglutide, significant decreases in weight from baseline were observed for both (−2.90 kg; p < 0.0001) and (−3.61 kg; p < 0.001), respectively.
In summary, weight loss observed among GLP-1 receptor agonists has been similar, on average ranging from 1.5 to 3 kg, with the exception of albiglutide which has shown less weight loss. This weight loss is attenuated when GLP-1 receptor agonists are combined with glucose-lowering agents known to cause weight gain (i.e. TZDs and SUs).
Source...