Impact of semaglutide with sleeve gastrectomy on blood glucose control and metabolism in obese type 2 diabetics

Abstract

BACKGROUND

Obesity and type 2 diabetes mellitus (T2DM) represent a major global health challenge. Although sleeve gastrectomy (SG) effectively induces weight loss and improves glycemic control, long-term outcomes can be limited by weight regain and metabolic fluctuations. Semaglutide, a glucagon-like peptide-1 receptor agonist, complements surgical effects through glucose-lowering and weight-loss mechanisms. We hypothesize that combining SG with semaglutide postoperatively will yield superior and more sustained improvements in glycemic control, weight reduction, and metabolic parameters compared to surgery alone, addressing a critical gap in the long-term management of obese T2DM patients.

AIM

To assess how SG and semaglutide affects metabolic markers and blood glucose control rate in individuals with T2DM and obesity.

METHODS

This retrospective cohort study analyzed 80 obese patients with T2DM admitted between December 2022 and June 2025. Patients included observation group (n = 40, SG plus semaglutide) and control group (n = 40, SG alone). We compared postoperative glycemic control rates and changes in fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, body mass index, homeostasis model assessment of β-cell function, and homeostasis model assessment of insulin resistance.

RESULTS

The observation group had a greater percentage of blood glucose control following therapy than the control group. When compared to pre-treatment levels, both groups’ fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and body mass index significantly decreased, with the observation group experiencing a larger reduction (P < 0.05). Simultaneously, the observation group demonstrated superior improvement in homeostasis model assessment of β-cell function and a greater reduction in homeostasis model assessment of insulin resistance compared to the control group (P < 0.05). The incidence of adverse outcomes after surgery did not differ significantly according to statistical analysis between the two groups (P > 0.05).

CONCLUSION

SG paired with semaglutide significantly improves the rate of blood glucose control in obese patients with T2DM, demonstrating superior metabolic benefits and islet function enhancement compared to surgery alone.

Key Words: Sleeve gastrectomy; Semaglutide; Obesity; Type 2 diabetes mellitus; Blood glucose control rate; Metabolic parameters

Core Tip: This retrospective cohort study in Chinese patients with obesity and type 2 diabetes mellitus found that adding semaglutide after sleeve gastrectomy, compared to surgery alone, significantly improved short-term diabetes remission and metabolic indicators (glucose, lipids, weight, islet function) without extra safety risks. The results demonstrate synergy between surgery and glucagon-like peptide-1 receptor agonist therapy, supporting an integrated “surgery plus postoperative drug intensification” model to address suboptimal or declining long-term outcomes. This offers an evidence-based treatment intensification option for optimizing management in clinical practice.

INTRODUCTION

In recent years, overweight and obesity have become increasingly common worldwide, posing a serious public health concern. Statistics indicate that Obesity and overweight prevalence among the Chinese population was 11.24% and 34.29%, respectively, in 2022[1]. Extensive epidemiological evidence shows that body weight exceeding the normal range, particularly in cases of pre-obesity or obesity, greatly raises the chance of acquiring a number of chronic illnesses, including type 2 diabetes mellitus(T2DM)[2]. The core pathophysiological mechanism involves excess adipose tissue inducing chronic inflammation and altering adipokine secretion, which leads to pronounced insulin resistance. Under these conditions, the physiological efficacy of insulin is severely compromised, impairing glucose homeostasis and ultimately progressing to clinically significant T2DM[3]. Current clinical interventions for obesity combined with T2DM include lifestyle management, pharmacotherapy, and metabolic surgery. Among these, bariatric and metabolic surgery – particularly sleeve gastrectomy(SG) – is regarded as an important option for treating moderate-to-severe obesity with T2DM due to its remarkable and sustained effects on weight loss and glucose metabolism improvement[4]. SG is a minimally invasive bariatric procedure that reshapes the stomach into a narrow, tubular sleeve to reduce its capacity, thereby limiting food intake and promoting weight reduction[5]. The early postoperative weight-loss effect of SG is significant, typically stabilizing within the first year after surgery. However, clinical practice has observed that while marked weight loss and rapid glucose remission are evident in the early postoperative period, some patients may subsequently experience weight regain and fluctuations in blood glucose levels. This phenomenon suggests that relying solely on surgical intervention may be insufficient to maintain long-term metabolic homeostasis. Therefore, exploring postoperative adjuvant treatment strategies to consolidate surgical outcomes and improve long-term control rate is of great importance[6]. Semaglutide is a novel long-acting glucose-lowering medication that effectively lowers blood glucose by increasing insulin production, suppressing glucagon secretion, and lowering glucose levels. It also suppresses central hunger and delays gastric emptying, which results in an independent weight-loss effect[7]. This article aims to systematically evaluate the clinical efficacy of combining SG with semaglutide in treating individuals with diabetes who are also obese, investigating the effects of this approach on postoperative blood glucose control and related metabolic parameters, thereby providing robust evidence for developing optimized, personalized comprehensive treatment strategies in clinical practice.

MATERIALS AND METHODS

Research object

The observation group consisted of 80 clients with obesity worsened by having T2DM who came to our hospital between December 2022 and June 2025. These patients were split into two groups, each consisting of 40 cases, based on variations in clinical intervention. Comparability was demonstrated by statistical comparison, which showed that demographic data, including age and gender, were not significantly different in each of the groupings (P > 0.05).

Exclusion and inclusion criteria

Inclusion criteria: (1) Being at least eighteen years old; (2) Fulfilling the World Health Organization’s T2DM diagnostic criteria[8]; (3) Meeting the clinical definition and diagnostic criteria for obesity[9]; and (4) Patients undergoing primary bariatric surgery.

Exclusion criteria: (1) Patients with dysfunction of major organs (e.g., liver, kidney); (2) Patients allergic to the drugs used in this trial or intolerant to surgery due to physical condition; (3) Patients with psychiatric disorders or cognitive dysfunction; (4) Women who are nursing or pregnant; (5) Individuals with acute-phase complications; (6) Those who have undergone insulin treatment in the previous three months; (7) Patients with acute cerebrovascular diseases, such as stroke; (8) Clients who have had any type of cancer; and (9) Clients with infectious or autoimmune diseases.

Elimination criteria: (1) Patients found to meet any exclusion criteria after enrollment; and (2) Patients whose complete baseline or clinical data could not be obtained.

Methods

Control group: The control group underwent SG. Patients were positioned supine. Three small incisions were made around the umbilicus and approximately 10 cm above the umbilicus along both midclavicular lines. Trocars measuring 10 mm, 5 mm, and 12 mm in diameter were sequentially inserted. The gastrocolic ligament and associated tissues were carefully dissected and divided to fully expose the gastric fundus and posterior gastric wall. Next, an oral 36 Fr bougie was inserted. Starting approximately 4-5 cm from the pylorus, resection proceeded along the greater curvature toward the proximal stomach using a straight stapler until reaching a point about 1.5 cm to the left of the angle of His, completely removing the gastric wall of the greater curvature, including the fundus, thereby creating a sleeve-shaped stomach with a volume of approximately 100 mL. The resection margin was oversewn with a continuous seromuscular layer using absorbable sutures. After confirming the absence of active bleeding at the surgical site, the abdominal cavity was closed in layers.

Observation group: The observation group underwent SG combined with semaglutide therapy. Semaglutide (Specification: 3 mL; Novo Nordisk China Pharmaceuticals Ltd.; National Medicine Approval Number: SJ20210015) was administered once weekly at a dose of 0.25 mg via subcutaneous injection. After four weeks of treatment, the dosage was increased to 0.5 mg once weekly. The treatment duration for both groups was 12 weeks.

Observation indicators

Blood glucose control rate: Refers to the percentage of cases with blood glucose levels reaching the standard after treatment among all follow-up subjects. The definition of blood glucose standard conditions is glycated hemoglobin (HbA1c) < 7%[10].

Glucose metabolism indicators: Before and after a 12-week course of therapy, each participant had 3 mL of blood from the veins collected while they were fasting. Concentrations of fasting plasma glucose, 2-hour postprandial glucose (2hPG), and HbA1c were measured using the hexokinase method. This analysis was performed on plasma samples obtained after a 15-minute spin at 3000 rotations a minute.

Lipid metabolism indicators and body mass index: Serum concentrations of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were measured using a fully automatic clinical chemistry platform. These assessments were performed at two time points: (1) Before treatment initiation; and (2) After a twelve-week therapeutic intervention. For all study participants, body mass index (BMI) was calculated. This index, derived from individual weight and height.

Pancreatic islet function: Islet function was assessed in every group prior to and following treatment, including the homeostasis model assessment of β-cell function (HOMA-β) and the homeostasis model assessment of insulin resistance (HOMA-IR).

Incidence of adverse events following surgery: The occurrence of postoperative gastrointestinal discomfort, hypoglycemia, incision infections, and pruritus at the local injection site was recorded in both groups.

Statistical analysis

The entirety of the investigation’s results was processed using the data analysis application SPSS 21.0. The t-test was used to evaluate intergroup comparisons, and measurement data are expressed as mean ± SD. The n (%) is used to characterize count data, and the χ² test was used to evaluate intergroup differences. A significance level of less than 0.05 was deemed to be significant.

RESULTS

Comparison of general characteristics between the two groups

As shown in Table 1, there was little difference between both groupings (P > 0.05).

Table 1 Comparison of general data between the two patient groups (n = 40), n (%)/mean ± SD.

Group	Gender		Age (years)	Type 2 diabetes mellitus duration (years)	Number of glucose-lowering agents
	Male	Female			Biguanides	Sulfonylureas
Control group	24 (60.00)	16 (40.00)	54.13 ± 2.52	8.33 ± 1.75	40	27 (67.50)
Observation group	21 (52.50)	19 (47.50)	54.05 ± 3.26	8.53 ± 1.91	40	23 (57.50)
Test statistic	0.457		0.115	-0.489	-	0.853
P value	0.499		0.909	0.626	-	0.356

Comparison of blood glucose control rate between the two groups

Following therapy, the control group’s blood glucose control rate was 10.00%, while the observation group’s was 62.50%. There was a statistically significant difference between both groupings (P < 0.05; Table 2).

Table 2 Comparison of blood glucose control rate between the two groups.

Group	Number of cases	Number of people meeting the standard	Blood glucose control rate (%)
Control group	40	8	20.00
Observation group	40	38	95.00
χ² value			46.036
P value			< 0.001

Comparison of glucose metabolism indicators between the two groups

After treatment, levels of fasting plasma glucose, 2hPG, and HbA1c decreased in both groups. The observation group experienced a greater decline than the control group, and the within-group variation was statistically significant (P < 0.05; Table 3).

Table 3 Comparison of glucose metabolism indicators between the two groups (n = 40), mean ± SD.

Group	Glycated hemoglobin (%)		Fasting plasma glucose (mmol/L)		2-hour postprandial glucose (mmol/L)
	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment
Control group	8.95 ± 0.98	7.51 ± 0.84	10.12 ± 1.32	8.97 ± 1.25	14.87 ± 1.26	10.37 ± 1.69
Observation group	8.70 ± 1.04	6.13 ± 0.56	9.80 ± 1.69	6.04 ± 0.89	14.66 ± 1.67	8.52 ± 1.21
t value	1.099	8.642	0.944	12.094	0.626	5.615
P value	0.275	< 0.001	0.348	< 0.001	0.533	< 0.001

Comparison of lipid metabolism indicators and BMI between the two groups

After treatment, both groups’ TC, TG, LDL-C, and BMI dropped from pre-intervention levels. There was a statistically significant variation between the two categories, with the observation one seeing greater declines than the control one (P < 0.05; Table 4).

Table 4 Comparison of lipid metabolism indicators and body mass index between the two groups (n = 40), mean ± SD.

Group	Total cholesterol (mmol/L)		Triglycerides (mmol/L)		Low-density lipoprotein cholesterol (mmol/L)		Body mass index (kg/m2)
	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment
Control group	5.92 ± 0.53	5.19 ± 0.52	1.95 ± 0.31	1.72 ± 0.34	3.14 ± 0.51	2.27 ± 0.37	32.98 ± 1.96	30.74 ± 1.26
Observation group	5.87 ± 0.67	4.02 ± 0.37	2.07 ± 0.37	1.21 ± 0.27	3.26 ± 0.48	1.58 ± 0.24	32.66 ± 1.87	28.09 ± 0.59
t value	0.334	11.633	-1.505	7.459	-1.089	10.010	0.747	12.021
P value	0.739	< 0.001	0.136	< 0.001	0.279	< 0.001	0.458	< 0.001

Comparison of pancreatic islet function between the two groups

Both groups had a rise in HOMA-β during treatment, although the observation one saw a larger increase than the control one. Both groups had a drop in HOMA-IR, although the observation group saw a larger decline than the control one. The results showed mathematically significant variations between the two categories (P < 0.05; Table 5).

Table 5 Comparison of pancreatic islet function between the two groups (n = 40), mean ± SD.

Group	Homeostasis model assessment of β-cell function		Homeostasis model assessment of insulin resistance
	Before treatment	After treatment	Before treatment	After treatment
Control group	1.89 ± 0.35	6.24 ± 0.69	3.79 ± 0.52	2.61 ± 0.36
Observation group	1.95 ± 0.42	7.64 ± 0.77	3.83 ± 0.67	2.08 ± 0.24
t value	-0.724	-8.583	-0.354	7.610
P value	0.471	< 0.001	0.725	< 0.001

Comparison of unfavorable events following surgery rates between the two groups

The percentage of cases of adverse events after surgery did not differ significantly between the two groupings (P < 0.05; Table 6).

Table 6 Comparison of unfavorable events following surgery rates between the two groups, n (%).

Group	Number of cases	Gastrointestinal discomfort	Hypoglycemia	Incisional infection	Local injection pruritus	Complication rate
Control group	40	2 (5.00)	1 (2.50)	1 (2.50)	1 (2.50)	5 (12.50)
Observation group	40	1 (2.50)	1 (2.50)	1 (2.50)	0 (0.00)	3 (7.50)
χ² value						1.885
P value						0.901

DISCUSSION

A complicated pathogenic process characterizes obesity, a chronic metabolic illness affecting several systems. It has been found to be a major risk factor for T2DM development and progression[11]. Concurrently, insulin resistance linked to adiposity and dysregulation of glucose and lipid metabolism are common mechanisms underlying the development of non-alcoholic fatty liver disease[12] and cardiovascular disorders[13], among other comorbidities. In the therapeutic treatment of T2DM and obesity, lifestyle modifications alone or conventional glucose-lowering medications often prove inadequate for achieving long-term, stable weight reduction and glycemic control[14]. SG, a widely adopted bariatric procedure, offers advantages such as relative technical simplicity, a lower complication rate, and preservation of gastrointestinal continuity[15]. By restricting gastric volume and influencing gastrointestinal hormone secretion, SG has become a successful surgical treatment for T2DM and obesity[16]. Nevertheless, the initial instability in metabolic parameters post-surgery suggests that adjunctive pharmacological intervention is important for consolidating and enhancing long-term therapeutic outcomes[17]. This study found that combining semaglutide with SG, compared to surgery alone, led to more significant improvements in patients’ glycemic parameters (FBG, 2hPG, HbA1c), lipid profile (TC, TG, LDL-C), BMI, and pancreatic islet function indices (HOMA-β, HOMA-IR), without an observed increase in safety risks. These findings provide evidence supporting the application of this combined regimen.

The data from this study indicate that, for individuals with T2DM who are also overweight, the combination of SG and semaglutide, compared to surgery alone, more effectively regulates blood glucose and lipid levels and promotes a reduction in BMI within 12 weeks postoperatively. The underlying mechanisms may involve the following aspects: (1) SG, by resecting a large portion of the gastric fundus, significantly reduces ghrelin production and limits food intake, thereby inducing weight loss and initially alleviating metabolic stress[18]. While reducing total body fat, the procedure also decreases visceral fat accumulation. The reduction in liver fat content further suppresses the secretion of very-low-density lipoprotein TG, promoting hepatic lipid and lipoprotein metabolism and thus improving the overall lipid profile[19]. Furthermore, the anatomical changes induced by the surgery can modulate adipokine and related hormone levels, further influencing lipoprotein and lipid metabolic processes[20]; (2) In addition to increasing insulin secretion, semaglutide, a glucagon-like peptide-1 receptor agonist used for precision glycemic control, also suppresses glucagon release in a glucose-dependent way. Additionally, it enhance the utilization of glucose by peripheral tissues and other multiple pathways, synergistically improving the overall metabolic status[21]. Simultaneously, the drug enhances weight control through central appetite suppression and delayed gastric emptying[22]; and (3) The combined application of SG and semaglutide exerts synergistic effects via dual pathways – surgical intervention and pharmacological neuroendocrine modulation – improving insulin resistance and increasing the fundamental effectiveness of weight reduction. The co-regulation of lipid metabolism through more significant weight reduction and improved insulin sensitivity may explain the combined regimen’s superior performance in lowering TG and LDL-C[23].

Moreover, based on the results of the study, participants in the combined treatment group exhibited a more significant decline in HOMA-IR and a greater increase in HOMA-β compared to the control group. This suggests that the treatment plan promotes the functional recovery of pancreatic β-cells and enhances peripheral tissue sensitivity to insulin. HOMA-IR, calculated using fasting blood glucose and fasting insulin levels, serves as an indirect measure of insulin resistance and typically indicates a reduction in insulin resistance when decreased[24]. Conversely, HOMA-β, which assesses the insulin-secretory capacity of β-cells, generally reflects improvement or recovery in β-cell function when increased[25]. These findings align with previously reported effects of semaglutide in improving islet function and reducing insulin resistance[26].

The data of this study shows that for obese patients with T2DM, after SG, the combined use of smeglutide can significantly improve the rate of reaching the standard of blood glucose control 12 weeks after surgery compared with simple surgery. This suggests that initiating semaglutide promptly, based on the early metabolic improvements from SG, can produce synergistic effects, leading to more effective glycemic control. Mechanistically, SG primarily induces initial weight loss and improves related metabolic parameters by restricting food intake and modulating gastrointestinal hormones. Through a number of processes, such as enhanced insulin secretion, delayed stomach emptying, and appetite suppression, semaglutide amplifies these metabolic advantages. The combination likely increases the likelihood of blood glucose control at an earlier postoperative stage by more rapidly and comprehensively alleviating insulin resistance and enhancing β-cell function. It’s crucial to remember that diabetic remission must last. Literature reports indicate that some patients may experience weight regain and worsening glycemic control following SG[27]. Restricted by the study’s comparatively brief period of follow-up, the intervention effect of the combined strategy on such long-term risks remains unclear. The role of semaglutide in maintaining long-term weight stability and glycemic control holds promise for consolidating the long-term efficacy of surgery, but this requires further observation and confirmation through extended follow-up.

The results showed that there was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group, and no serious adverse events occurred. This preliminary indication suggests that the addition of semaglutide in the short term after surgery did not result in unexpected safety risks. However, the sample size of this study is small, the absolute number of observed adverse events is small, and the statistical testing power is limited. Its safety still needs to be further verified by expanding the sample size and extending the follow-up time. This study also has several limitations. First, selection bias may be introduced by its retrospective, single-center design and somewhat small sample size. Second, the current follow-up period is insufficient to adequately compare the differences between combined therapy and surgery alone in terms of blood glucose control status, weight stability, and complication rates over the medium to long term (e.g., beyond one year). Finally, the study primarily focused on changes in metabolic indicators; the effects of this combined intervention on potential mechanisms, such as the gut microbiome and key inflammatory markers, were not systematically investigated. Future studies should use prospective, multicenter, large-scale randomized controlled trials with lengthy follow-up periods to more thoroughly evaluate the long-term effectiveness and safety of combining SG with semaglutide. These investigations should also look at the pharmacological and molecular processes that underlie their synergistic effects.

CONCLUSION

In conclusion, the combined application of SG and semaglutide in individuals with T2DM and fat can more effectively decrease weight loss, improve glucose and lipid metabolism, enhance pancreatic islet function, and increase the probability of blood glucose control in the short term, without significantly increasing risks during the observation period of this study. This comprehensive therapy provides a new clinical pathway for metabolic management in patients with obesity and T2DM, while its consequences that last and mechanisms of action require further in-depth investigation.