Comparing the Efficacy of Liraglutide and Semaglutide on Weight Loss: Experience from the Middle East Gulf Region and Literature Review

Abstract

Objective: Available data comparing the efficacy of liraglutide and semaglutide in managing weight loss is limited. The objective of this study was to compare efficacy of both drugs on weight loss. Methods: A retrospective observational cohort study conducted at our quaternary care hospital from June 2018 to July 2022. The study included adults who received either liraglutide or semaglutide during the study period. The primary outcome was weight loss, while secondary outcomes included effects on HbA1c levels and lipid profile. Results: A total of 366 patients were analyzed (122 on liraglutide, 244 on semaglutide). The groups were comparable in mean age (51.00 ± 11.55 vs 51.16 ± 12.35 years, P = 0.521) and baseline mean weight (94.7 ± 19.5 vs 94.6 ± 19.9 kg, P = 0.989). After a median follow-up of 10 (6-17) months for the liraglutide group and 7.5 (6-11) months for the semaglutide group (P < 0.001), the resultant weights were 90.8 ± 19.6 kg for the liraglutide group and 91.1 ± 19.8 kg for the semaglutide group (P < 0.001) when comparing each group to its baseline separately. When comparing the weight loss achieved in each group, liraglutide achieved a median weight loss of −4 (−7 to 0) kg versus −3 (−6 to 0) kg for semaglutide (P = 0.867). The reduction in HbA1c levels with liraglutide was significantly less than with semaglutide: −0.2 (−0.5 to 0.3) versus −0.5 (−1.1 to 0.1), respectively, (P = 0.003). Both drugs significantly lowered LDL and triglycerides. Multivariable linear regression analysis confirmed no significant difference between the drugs [B −0.577, 95% CI −1.87 to 0.7; P = 0.38], while baseline weight, diabetes, and SGLT2 inhibitors were significant factors affecting weight. Conclusion: Both liraglutide and semaglutide were effective in reducing weight, with no significant difference between the two drugs. However, semaglutide was more effective in reducing HbA1c levels.

Background

Obesity, defined as the excessive accumulation of fat in various parts of the body or organs represents a worldwide health issue. ¹ In fact, obesity is a chronic, progressive, relapsing and multifactorial condition caused mainly by a constant imbalance in energy expenditure causing nutrient signal disruption. ² The diagnosis of obesity relies on the body mass index (BMI) cut off and the relationship between body weight, fat distribution patterns, and visceral fat. ³ Obesity prevalence is constantly increasing and is expected to reach 14% of men and 20% of women who will eventually develop clinical obesity by 2030. Based on the World Obesity Federation reports, an alarming prevalence of obesity was noted in countries with high socioeconomic status that are at a greater risk of experiencing an increased prevalence of obesity. ⁴ Thus, approximately two-thirds of the adult population in the United States was either obese or overweight ⁵ with 42.4% of adults with a BMI ≥ 30 kg/m², while 20.9% of youth had a BMI ≥ 30 kg/m². ⁵

The prevalence of obesity defined as body mass index (BMI) ≥ 30 kg/m² and overweight BMI ≥ 25 to 29.9 kg/m² was lately assessed in the UAE. It showed as high as 17.8% among adults in the emirate of Dubai. The highest obesity rates were reported among women (21.6%) and UAE-nationals (39.6%). Moreover, 39.8% of the population was considered overweight. ⁶

The glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the intestines after eating that stimulates insulin secretion based on blood glucose levels, helping reduce the risk of hypoglycemia. Therefore, GLP-1 receptor agonists (GLP-1RAs), such as liraglutide and semaglutide act by reducing the blood sugar levels and have been approved for use in the treatment of type 2 diabetic adults. ⁷ Both medications have also been used for weight loss, as GLP-1 helps lower HbA1c, reduce obesity, and prevent complications of chronic high blood sugar by curbing appetite and slowing gastric emptying.^8,9

Semaglutide and liraglutide are both subcutaneous long-acting GLP-1 RAs that significantly reduce the HbA1c level.^10,11 Liraglutide has been approved as an antidiabetic in 2010 ¹² and as a weight loss medication in 2014 ¹³ at a dose of 3 mg once daily, ¹¹ whilst semaglutide 1 mg was approved as an antidiabetic in 2017. ¹⁴ As the current literature has shown, semaglutide has beneficial effects in weight loss. ⁸ Additionally, semaglutide has been recently approved by the US Food and Drug Administration (FDA) for use in weight reduction at a dose of 2.4 mg. ¹⁵ Another study was conducted to compare the efficacy and safety of the semaglutide dose range of 0.05 to 0.4 mg compared with liraglutide 3.0 mg and placebo for weight loss in patients with obesity. Semaglutide at doses of 0.2 mg/day and above resulted in a higher percentage of weight reduction when compared to liraglutide 3 mg/day and the placebo. ¹ However, there are no clinical outcome data was reported from the Middle East Gulf region. Hence, the purpose of this study was to further assess the effectiveness of the used doses of semaglutide and liraglutide, for weight loss in both diabetic and nondiabetic patients with a BMI ≥ 25 kg/m² baseline weight.

Methods

Study Population

A retrospective cohort observational study was conducted at our quaternary care hospital from June 2018 to July 2022. The study included adult patients who received either liraglutide or semaglutide during the study period for any indication (i.e. diabetes or weight loss), excluding those who received either drug for less than 3 months. The study was approved by the hospital’s research ethics committee, with a consent waiver granted due to its retrospective design.

Demographic and baseline characteristics were collected, along with all relevant laboratory data prior to drug administration. Laboratory findings following drug administration, as well as any adverse events, were documented. The primary outcome was the efficacy of each drug in promoting weight loss, while secondary outcomes included effects on HbA1c levels and lipid profiles.

Data Analysis

The normality and distribution of the data were assessed using the Shapiro-Wilk test and by visually inspecting the distribution of variables (histogram). Data was presented as mean ± SD for normally distributed data or as median (IQR) for non-normally distributed data. Descriptive statistics for categorical variables was expressed as proportions. Comparisons of values between independent continuous variables were conducted using the Student’s t-test or the Mann–Whitney U test, as appropriate. Comparisons of values between dependent continuous variables were conducted using the paired t-test or the Wilcoxon Signed Rank test, as appropriate. Discrete data were analyzed using the χ² test or Fisher exact test for small numbers for independent variables, while dependent variables were compared using McNemar’s test. Multivariable linear regression analysis was conducted to identify independent factors affecting weight loss. A two-sided P-value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS statistical package version 29 for Microsoft Windows (IBM, Armonk, NY).

Results

A total of 366 patients met the inclusion criteria, with 122 having received liraglutide and 244 having received semaglutide during the study period. The mean age was 51.00 ± 11.55 years in the liraglutide group and 51.16 ± 12.35 years in the semaglutide group (P = 0.521), with 85 (69.7%) females in the liraglutide group and 130 (53.3%) in the semaglutide group. The baseline BMI was 35.6 ± 6.3 kg/m² (mean weight 94.7 ± 19.5 kg) in the liraglutide group and 35 ± 7 kg/m² (mean weight 94.6 ± 19.9 kg) in the semaglutide group. Demographics and baseline characteristics, including medications, are presented in Table 1.

Table 1.

Baseline Characteristic of the Study Patients.

Variables	Liraglutide (n = 122)	Semaglutide (n = 244)	P-value
Age	51.00 ± 11.55	51.16 ± 12.35	0.521
Gender (females)	85 (69.7%)	130 (53.3%)	0.003
Weight (kg)—start	94.7 ± 19.5	94.6 ± 19.9	0.989
BMI (kg/m2)—start	35.6 ± 6.3	35 ± 7	0.231
Charlson comorbidity index	2 (1–4)	2 (1–4)	0.079
Hypertension	60 (49.6%)	153 (62.7%)	0.18
Diabetes	92 (75.4)	226 (92.6)	<0.001
Diabetes			<0.001
Diabetic Type 2	89 (73%)	222 (91%)
Diabetic Type 1	2.5 ( 3%)	1.2% (3)
Pre-diabetic	4 (3.3%)	8 (3.3%)
Non-diabetic	26 (21.3%)	10 (4.1%)
Dyslipidemia	82% (100)	87.7% (214)	0.154
Renal disease	15 (12.3%)	37 (15.2%)	0.527
Kidney function			0.199
Stage 3 chronic kidney disease	7 (50%)	15 (38.5%)
Stage 4 chronic kidney disease	3 (21.4%)	2 (5.1%)
Stage 5 on chronic kidney disease on dialysis	2 (14.3%)	13 (33.3%)
Liver disease	13 (10.7%)	34 (13.9%)	0.412
Angiotensin-converting enzyme inhibitors	9 (7.4%)	0 (0%)	<0.001
Angiotensin receptors blockers	27 (22.1%)	107 (43.9%)	<0.001
Angiotensin receptor-neprilysin inhibitor	5 (4.1%)	9 (3.7%)	1
Beta-blockers	23 (18.9%)	68 (27.9%)	0.072
Calcium channel blockers	36 (29.5%)	60 (24.6%)	0.316
Potassium sparing diuretics	5 (4.1%)	10 (4.1%)	1
Loop diuretics	12 (9.8%)	19 (7.8%)	0.552
Thiazide diuretics	8 (6.6%)	27 (11.1%)	0.191
Metformin	80 (65.6%)	179 (73.4%)	0.144
Dipeptidyl peptidase 4 inhibitors	9 (7.4%)	26 (10.7%)	0.352
Linagliptin	1 (11.1%)	10 (37%)	0.223
Sodium-glucose linked transporter 2 inhibitors	32 (26.2%)	119 (48.8%)	<0.001
Dapagliflozin	3 (9.4%) (3)	29 (24.4%)	0.087
Sulphonylureas	17 (13.9%)	32 (13.1%)	0.871
Gliclazide	14 (82.4%)	28 (87.5%)	0.681
Meglitinides	1 (0.8%)	2 (0.8%)	1
Repaglinide	100% (1)	100% (3)	NA
Thiazolidinediones	0 (0%)	3 (1.2%)	0.554
Pioglitazone	100% (3)	100% (3)	NA
Statins	80 (65.6%)	187 (76.6%)	0.033
Fibrates	?	?	?
Ezetimibe	8 (6.6%)	0 (0%)	<0.001
PCSK9_Inhibitors	2 (1.6%)	0 (0%)	0.111
Insulin	25 (20.7%)	97 (39.8%)	<.001
Glargine	16 (64%)	59 (62.1%)	1
Aspart	9 (69.2%)	37 (57.8%)	0.544

The median follow-up period was 10 months (6-17) for the liraglutide group and 7.5 months (6-11) for the semaglutide group (P < 0.001). The resulting weights were 90.8 ± 19.6 kg for the liraglutide group and 91.1 ± 19.8 kg for the semaglutide group, both showing significant reductions compared to their respective baselines (P < 0.001) (Table 2). Additionally, HbA1c levels were significantly reduced in both groups. In the liraglutide group, HbA1c decreased from 6.6% (5.7-7.9) to 6.3% (5.6-7.3) (P = 0.017), while in the semaglutide group, it decreased from 7.5% (6.4-8.8) to 6.8% (5.8-8.05) (P < 0.001). Furthermore, LDL cholesterol levels significantly decreased in both groups: from 2.97 (2.13-3.61) to 2.51 (1.73-3.43) in the liraglutide group (P = 0.023), and from 2.39 (1.73-3.24) to 2.15 (1.56-3.02) in the semaglutide group (P = 0.002). A detailed comparison of outcomes to baseline values is provided in Table 2.

Table 2.

Outcomes Comparison for Each Drug Versus Baseline.

Variables	Baseline (liraglutide n = 122)	Outcome (liraglutide n = 122)	P-value	Baseline (semaglutide n = 122)	Outcome (semaglutide n = 244)	P-value
Weight (kg)	94.7 ± 19.5	90.8 ± 19.6	<0.001	94.6 ± 19.9	91.1 ± 19.8	<0.001
Body Mass Index (kg/m2)	35.6 ± 6.3	34.1 ± 6.7	<0.001	35 ± 7	33.7 ± 6.9	<0.001
Systolic blood pressure	127 (119–137.5)	126 (118–136)	0.445	128 (117.2–136)	125 (115–135)	0.072
Diastolic blood pressure	76 (69.5–82)	77 (69.5–82)	0.744	76 (69–84)	75 (66–81)	0.006
Hemoglobin A1c%	6.6 (5.7–7.9)	6.3 (5.6–7.3)	0.017	7.5 (6.4–8.8)	6.8 (5.8–8.05)	<0.001
Random blood sugar level (mmol/L)	7.4 ± 2.9	7.1 ± 2.7	0.422	8.7 ± 3.7	8 ± 3.6	<0.001
Total-cholesterol (mmol/L)	4.4 (3.6–5.2)	4.1 (3.3–5.0)	0.374	4.01 (3.2–4.8)	3.8 (3.1–4.7)	0.032
HDL cholesterol (mmol/L)	1.26 (0.98–1.49)	1.25 (1.06–1.52)	0.08	1.14 (0.97–1.34)	1.14 (0.96–1.37)	0.77
LDL cholesterol (mmol/L)	2.97 (2.13–3.61)	2.51 (1.73–3.43)	0.023	2.39 (1.73–3.24)	2.15 (1.56–3.02)	0.002
Triglyceride (mmol/L)	1.41 (1–1.95)	1.28 (0.96–1.91)	0.028	1.54 (1.12–2.26)	1.39 (0.99–1.90)	<0.001
Estimated glomerular filtration rate (mL/min/m2)	57.9 ± 8.2	57.7 ± 8.8	0.635	58.6 ± 4.6	58.2 ± 6.2	0.344
Serum creatinine (mmol/L)	64.5 (51.2–83.7)	61 (51–76)	0.93	70.5 (55–84.7)	69 (55–85.7)	0.295
Creatinine clearance (mL/min)	143 (108.7–174.2)	140 (102.7–162)	<0.001	126 (93.5–180)	121 (90.5–176)	<0.001
Drug dose (mg)	0.6 (0.6–1.8)	1.8 (1.8–3)	<0.001	0.25 (0.25–0.5)	1 (0.5–1)	<0.001
Metformin daily dose (mg)	2000 (1000–2000)	1000 (0–2000)	0.301	2000 (1500–2000)	1500 (0–2000)	0.344
Long-acting insulin dose (units)	25 (20–35)	25.5 (18.5–36)	0.504	30 (16–40)	30 (16–40)	0.457
Short acting insulin dose (units)	30 (15–44)	30 (17–44)	1	30 (23–57)	30 (18–60)	0.663

When comparing the weight loss between the groups (Table 3), there was no significant difference between the liraglutide and semaglutide groups: −4 (−7 to 0) kg versus −3 (−6 to 0) kg, respectively (P = 0.867). However, the reduction in HbA1c was significantly greater with semaglutide compared to liraglutide: −0.5 (−1.1 to −0.1) versus −0.2 (−0.5 to 0.3) (P = 0.003), respectively. Additionally, there was no significant difference between the two drugs in reducing LDL cholesterol. Table 3 presents a comparison of both drugs across the measured outcomes.

Table 3.

Variables and Drugs at Baseline and at the End of the Study.

Variables	Liraglutide (n = 122)	Semaglutide (n = 244)	P-value
Follow up in months	10 (6 to 17)	7.5 (6 to 11)	<0.001
Weight—difference (kg)	−4 (−7 to 0)	−3 (−6 to 0)	0.867
Body Mass Index (kg/m2)—difference	−1.29 (−2.50 to 0)	−1.32 (−2.55 to 0)	0.982
Hb (A1c%)—difference	−0.2 (−0.5 to 0.3)	−0.5 (−1.1 to 0.1)	0.003
Serum plasma glucose (mmol/L)—difference	0 (−1.2 to 0.7)	−0.6 (−2.3 to 0.72)	0.088
T-cholesterol (mmol/L)—difference	0 (−0.72 to 0.36)	−0.07 (−0.56 to 0.38)	0.737
Systolic blood pressure—difference (mmHg)	−2 (−22 to 10)	−1 (−12.75 to 8)	0.653
Diastolic blood pressure—difference (mmhG)	−1 (−6.5 to 6.5)	−2 (−9 to 4.75)	0.198
Creatinine serum (mmol/L)—difference	0 (−5 to 5)	0 (−4.1 to 6.5)	0.631
Creatinine clearance (mmol/L)—difference	−9 (−20 to 3.2)	−5 (−19.2 to 6)	0.439
HDL cholesterol (mmol/L)—difference	0.01 (−0.04 to 0.10)	0 (−0.09 to 0.07)	0.118
LDL cholesterol (mmol/L)—difference	−0.13 (−0.80 to 0.24)	−0.11 (−0.56 to 0.26)	0.51
Triglycerides (mmol/L) —difference	−0.10 (−0.43 to 0.19)	−0.13 (−0.53 to 0.15)	0.61

Table 4 presents the findings from the multivariable linear regression analysis. The results did not show a significant difference between the two study drugs after adjusting for confounders such as baseline weight, diabetes status, baseline HbA1c, or insulin use [B −0.577, 95% CI −1.87 to 0.7; P = 0.38]. However, baseline weight, diabetes status, and the use of SGLT2 inhibitors (SGLT2is) were identified as significant factors influencing weight loss.

Table 4.

Multivariable Linear Regression Model Illustrating Factors Affecting Body Weight.

	Unstandardized coefficients	Standardized coefficients	95.0% confidence interval for B		Sig.
Variable	B	Beta	Lower bound	Upper bound
(Constant)	−3.067		−7.073	0.94	0.133
Semaglutide (Liraglutide reference)	−0.577	−0.014	−1.872	0.718	0.381
Baseline weight (kg)	0.965	0.97	0.934	0.996	<0.001
Diabetes	2.352	0.037	0.088	4.615	0.042
Hemoglobin_A1c% at Start	0.124	0.012	−0.262	0.511	0.528
Metformin	−1.239	−0.029	−2.677	0.199	0.091
Sodium/glucose cotransporter 2 Inhibitors	1.719	0.045	0.444	2.995	0.008
Insulin	1.136	0.029	−0.241	2.514	0.106

Note. R² = 92%.

Discussion

Our findings indicate that both liraglutide and semaglutide were effective in promoting weight loss and played a significant role in reducing both HbA1c and LDL levels in addition to their positive impact on patients’ lipid profiles. The linear regression indicated that both drugs did not differ significantly on promoting weight loss, however, patients with diabetes and those who were receiving SGLT2i’s presented with more pronounced effect on weight.

Our findings, based on a cohort from the Middle Eastern population in the UAE, are the first in the region to demonstrate comparable efficacy between semaglutide and liraglutide, at the studied doses, in achieving weight loss. These results align with the following two studies, the major clinical trials programs; SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and PIONEER (Peptide Innovation for Early Diabetes Treatment), that studied the use of 1.0 mg, once-weekly, subcutaneous and oral semaglutide variable doses, respectively, on participants with type 2 diabetes. As well as with the third major trial, STEP (Semaglutide Treatment Effect in People with Obesity) that examined the effects of 2.4 mg, once-weekly, subcutaneous semaglutide on patients with obesity. However, our results showed that in a mixed population of diabetic, prediabetic, and non-diabetic patients in the UAE, semaglutide and liraglutide demonstrated comparable clinical effects, with no evidence of superiority for either medication. Contrarily, all three, above mentioned, clinical trials demonstrated that semaglutide (injectable or oral) has superior efficacy compared with placebo and other antidiabetic medications in weight reduction, which led to the FDA’s approval of semaglutide for weight loss. The SUSTAIN trial has compared semaglutide with other long-acting GLP-1 RA, such as exenatide extended release, and has demonstrated that semaglutide was more efficacious in promoting body weight reduction. Furthermore, and unlike our results, the SUSTAIN 10 trial showed that semaglutide also held superiority over liraglutide. Semaglutide further showed superiority for the number of participants achieving a weight loss of ≥5%, and those achieving a weight loss of ≥10%. ¹⁶ The discrepancy observed in our results may be explained by the fact that the SUSTAIN and PIONEER trials included only diabetic patients, potentially highlighting greater efficacy of semaglutide specifically within a diabetic clinical context. Moreover, The SUSTAIN investigators have attributed semaglutide’s superior efficacy to its slightly modified, yet beneficial, structure which has a 94% homology with endogenous GLP-1. In fact, the addition of a fatty diacid chain at position 26 improved albumin binding. Furthermore, and of a general note, replacing alanine with α-aminoisobutyric acid at position 8 made semaglutide more resistant to breakdown by dipeptidyl peptidase-4, significantly extending its half-life and enabling once-weekly subcutaneous dosing, unlike liraglutide which requires daily administration. Thus, resulting in better compliance and patient satisfaction in patients with obesity when compared to any other medication.^10,17

Further evidence from the PIONEER clinical trial program highlighting semaglutide’s superiority investigated glycemic control and weight loss in patients with type 2 diabetes on oral semaglutide versus other oral anti-diabetic medications such as dipeptidyl peptidase-4 inhibitors (sitagliptin) and sodium-glucose co-transporter-2 inhibitors (empagliflozin). The PIONEER results indicated that semaglutide is currently the only oral anti-diabetic medication, within its drug class, all other GLP-1 RAs requiring administration via subcutaneous injection.^18,19 Moreover, it demonstrated oral simaglutide’s superiority when compared with other agents from the same drug class such as liraglutide.^18,20,21 Of note, in our study, the follow-up period for semaglutide was significantly shorter than that for liraglutide, which could have impacted our clinical findings. Therefore, the efficacy of semaglutide and liraglutide in reducing body weight observed in our study aligns with findings from major trials. However, semaglutide’s superiority was not clinically demonstrated in our patient cohort, as there was no significant difference in median weight or BMI change between the two groups from baseline to the end of the study. This disparity could, also be attributed to differences in the tested drug doses. At our institute, the median initial dose of semaglutide was 0.25 mg (0.25–0.5 mg) and increased to up to 1 mg (0.5–1 mg) by the end of the study. In contrast, the median initial dose of liraglutide was 0.6 mg (0.6–1.8) and increased to 1.8 mg (1.8–3 mg) by the study’s end. These doses were significantly lower than those used in the studies. Discrepancies may also stem from the shorter follow-up duration for the semaglutide group as this may have impacted the final body weight and HbA1C. Other outcomes, such as decreasing waist circumference and BMI, were also observed in the PIONEER study. ²⁰ Semaglutide’s effect was shown to be dose-dependent, with a 14 mg dose yielding the greatest reductions. ²¹ STEP was the most recent trial program to evaluate the efficacy of subcutaneous semaglutide as the only weight loss medication. Not all STEP results could be compared to our results as the majority of STEP participants were recruited based on BMI, excluding T2DM patients.^15,22-25 In our study, patients using either drug were included regardless of their diabetes status or type. In contrast, STEP 8 specifically enrolled adults with overweight or obesity without diabetes, aiming to compare the efficacy and adverse effect profiles of once-weekly subcutaneous semaglutide (2.4 mg) versus once-daily subcutaneous liraglutide (3.0 mg). This trial once again demonstrated the superiority of semaglutide in achieving weight loss compared to liraglutide. ²⁶ Despite this, our results showed a similar effect between the two drugs. These differences can likely be attributed to key distinctions in study design: our mixed population of both diabetic and non-diabetic patients, the exclusive inclusion of non-diabetic overweight or obese individuals in STEP 8, and the longer follow-up period in our study. These factors highlight the need for further investigation before applying our findings to similar patient populations in the region. While both drugs remain viable options, determining a clear preference between semaglutide and liraglutide requires additional research. A more recent 2023 open-label, prospective, randomized, parallel group-controlled trial investigated the effects, in clinical practice, of switching from liraglutide to semaglutide or dulaglutide on blood glucose, body weight, and the occurrence of adverse effects in a cohort of Japanese type 2 diabetic patients treated with liraglutide (0.6 or 0.9 mg), before being randomly assigned to the semaglutide or dulaglutide group (1:1).The semaglutide group showed a significant decrease in body weight (−2.6 to 3.6 kg, P = 0.0153), as opposed to the dulaglutide group who didn’t show any significant change (−0.1 to 2.7 kg, P = 0.8432). Body weight also showed significant difference between the groups (P = 0.0469). ²⁷

A 2024 systematic review and network meta-analysis that compared the effectiveness of a panel for GLP-1 RAs on T2DM patients’ glycemic control, body weight, and lipid profile has shown that the combination of semaglutide with cagrilintide resulted in the highest weight loss (mean difference −14.03 kg (95% confidence interval −17.05 to −11.00);, followed by tirzepatide (−8.47 kg (−9.68 to −7.26). ²⁸ In fact, 23 RCTs with 11,545 patients and four interventions (semaglutide 2.4 mg, semaglutide 1.0 mg, liraglutide 3.0 mg and liraglutide 1.8 mg) have demonstrated the significant efficacy of semaglutide 2.4 mg on achieving the best weight loss (−12.47 kg), followed by liraglutide 3.0 mg (−5.24 kg), semaglutide 1.0 mg (−3.74 kg) and liraglutide 1.8 mg (−3.29 kg) which is in accordance with our results showing efficacy in using both semaglutide and liraglutide on achieving weight loss. ²⁹

Additionally, the significant contribution of SGLT2i’s, administered concomitantly with GLP1 RAs, in reducing weight loss has demonstrated a novel finding in our study. In fact, to our knowledge, the clinical outcomes of using SGLT2i’s on weight loss was not assessed in correlation with other weight loss drugs or as concomitant treatment. In fact, studying the effect of SGLT2i’s, among other antidiabetic drugs on type 2 diabetic patients has been limited to assessing their muscle mass. ³⁰ Results have demonstrated both semaglutide (MD: −1.68, 95% CI: −2.84 to −0.52) and SGLT2i’s such as dapagliflozin (−0.53, −0.93 to −0.13), and canagliflozin (−0.90, −1.73 to −0.07) caused significant effect in decreasing fat when compared with the placebo, while Metformin did not show a significant decrease. Furthermore, a systematic review and network meta-analysis of sixty-one RCTs showed that GLP-1 RAs and SGLT-2i’s conferred greater extents in body weight reduction, achieving at least 5% of weight loss compared with placebo. The same analysis also reported that intraclass comparison, showed that semaglutide 2.4 mg showed the most effective interventions in losing body weight (MD: −11.51 kg, 95% CI −12.83 to −10.21). ³¹ These findings, however, reflect the combined effects of both drugs used simultaneously, whereas our results have demonstrated the clinical efficacy of the concomitant use of SGLT2i’s together with GLP1 RAs, on achieving weight loss while deploying linear regression to adjust for confounding factors.

In terms of glycemic control, evaluated by decreased HbA1c levels, the same meta-analysis mentioned above has demonstrated that the use of semaglutide 2.4 mg (MD = −1.48%, 95% CI [−1.93, −1.04]), semaglutide 1.0 mg (MD = −1.36%, 95% CI [−1.72, −1.01]), liraglutide 1.8 mg (MD = −1.23%, 95%Cl [−1.66, −0.80]) was more effective than placebo which also aligns with the results we report regarding both liraglutide and semaglutide similar efficacies, at the tested doses, in significantly attaining glycemic control. ²⁹ However, in other studies, semaglutide’s efficacy in promoting HbA1c level reductions showed superiority when compared with placebo ³² and with multiple antidiabetic medications, including insulin glargine, ¹⁶ sitagliptin, ³³ exenatide extended release (ER), ¹⁸ dulaglutide ³⁴ canagliflozin ³⁵ and liraglutide. ² Results have also denoted that oral semaglutide 7 mg and 14 mg showed more improvement in HbA1c levels compared with sitagliptin, however a 3 mg dose showed no clinically significant benefit. ³⁶ Successive clinical trials related to the PIONEER trial program continued to prove the significant decrease in both HbA1c while using oral semaglutide when compared with placebo.^{15,20-29,37-40} Glycemic control was assessed by evaluating changes in HbA1c levels from baseline to weeks 8, 16, and 26 post-treatment. A total of 30 patients who completed the study showed reduced HbA1c levels in the semaglutide treated group when compared to the dulaglutide group (−0.42 to 0.49% vs −0.00 – 0.34%, P = 0.0120) reflecting effective glycemic control. ²⁷ Once again, our results are in accordance with the trial results regarding the clinical efficacy of semaglutide in managing glycemic control and improving patient’s body weight in our studied population of diabetic, pre-diabetic and non diabetic patients. ²⁷ Moreover, the above-mentioned systematic review and network meta-analysis also reported semaglutide 2.4 mg was among the most effective interventions in decreasing HbA1c (MD: −1.49%, 95% CI −2.07 to −0.92), ³¹ which could explain the possible synergistic effect played by semaglutide and liraglutide together with administered SGLT2i’s in our cohort of studied patients. Furthermore, semaglutide has shown effectiveness in lowering the concentration of LDL (−0.16 mmol/L (−0.30 to −0.02)) and total cholesterol (−0.48 mmol/L (−0.84 to −0.11)) ²⁸ which aligns with reduction in LDL levels we demonstrated in our patient cohort highlighting a clinically meaningful outcome of the treatments. As a general note, our study presents relatively novel findings in the region, demonstrating that low yet effective doses of both semaglutide and liraglutide can reduce body weight and help control HbA1c and LDL levels. These effects were observed in a heterogeneous group of both diabetic and non-diabetic patients, in contrast to global studies that primarily involved diabetic populations using higher doses.

Study Limitations

Considering some disparities we have observed regarding the similar effects of liraglutide compared to semaglutide, while semaglutide showed superior efficacy on weight loss in all other studies compared to all GLP-1 RAs, we should highlight that our study presents with the inherit limitations of a retrospective observational study, therefore the relatively low number of patients reflects the low power to reach statistical significance to show semaglutide’s superiority in achieving better weight loss results. Moreover, our study didn’t account for any other weight loss interventions, such as a hypocaloric diet program or diet and exercise/lifestyle modification counseling and lifestyle modifications as a part of possible additional contributing factors to weight reduction. Furthermore, the lack of difference observed between the two drugs may be attributed to the difference in follow-up periods. Further studies addressing these comparisons are needed.

Conclusion

Both liraglutide and semaglutide were effective in reducing weight, with no significant difference between the two drugs. Further large-scale prospective studies are necessary to confirm these findings.