Efficacy of Dapagliflozin Combined with Lifestyle Intervention in Obesity Control.

Objective: To explore the best treatment of obesity in middle and old age.
Methods: 80 obese patients in our hospital from January 2020 to December 2021 were randomly divided into the control group and the intervention group according to the numerical table method. The control group was treated with lifestyle intervention, while the intervention group was treated with dapagliflozin combined with lifestyle intervention. The effects of body weight, body mass index (BMI), waist circumference, and blood lipids (LDL, HDL, TC, and TG) were measured and compared. Anxiety and depression scores were assessed using the 2018 Revised Anxiety and Depression Scale.
Results: There were no significant differences in body weight, BMI, and waist circumference between the control group and the intervention group before treatment. After treatment, the weight, BMI, and waist circumference of the intervention group were lower than those of the control group, and the difference was statistically significant (P < 0.05). After treatment, LDL, TC, and TG in the two groups were decreased, and HDL was significantly increased (P < 0.05). After treatment, the blood lipid level in the intervention group was significantly lower than that in the control group (P < 0.05). Anxiety and depression symptoms improved in both groups, and there were no serious adverse effects.
Conclusion: Dapagliflozin in combination with a lifestyle intervention effectively and safely treats excess weight in middle-aged and older adults, reverses obesity-related markers, and improves psychological symptoms. Its curative effect is better than that of using lifestyle intervention alone.

1. Introduction

Obesity has become one of the major health problems worldwide [1, 2]. Obesity, especially in middle-aged and older adults, is relatively difficult to treat and involves complex pathophysiology, including the interaction of socioeconomic, family, and personal factors [3, 4]. There is currently insufficient evidence to support any specific weight management regimen for the treatment of obesity in middle-aged and older adults. The most successful program so far is a combination of behavioral therapy and lifestyle modification therapy [5, 6]. But because these programs require family involvement and changes in established eating or activity habits, they are often intolerable and easily dropped out [6]. Studies have investigated the effectiveness of drug treatments, but the results are still suboptimal [7, 8]. Medications such as metformin or orlistat are not better than lifestyle interventions [9]. Dapagliflozin is a sodium-glucose cotransporter- (SGLT-) 2 inhibitor that improves blood glucose metabolism in patients by targeting glucose metabolism and inhibiting oxidase 2 (NOX2) and is currently widely used in the treatment of diabetes and obesity [10, 11]. Currently, in clinical trials, middle-aged and elderly people receive dapagliflozin mainly for the treatment of type 2 diabetes [12, 13]. A new multicenter randomized clinical trial by Aaron et al. evaluates the use of dapagliflozin in the treatment of obesity in the middle-aged and elderly [14]. This supports the use of drugs in the treatment of obesity in the middle-aged and elderly. However, no studies have evaluated the combined effect of the two treatment modalities. This study selected obese patients in our hospital since 2020 to give different treatments and observe the treatment results, in order to explore the best treatment plan for middle-aged and elderly obesity.

2. Methods

2.1. Patients

The diagnostic criteria for obesity are based on the classification criteria for overweight and obesity in China and the middle-aged and elderly recommended by the “China Academic Conference on Obesity in Middle-aged and Elderly” in 2003: body mass index (BMI) ≥ 24 kg/m2 was overweight, ≥28 kg/m2 was obese, waist ≥ 85 cm for men and ≥80 cm for women was abdominal obesity [15].

Inclusion criteria: (1) those aged between 35 and 70 years old, who have not received treatment intervention and meet the above diagnostic criteria can be included, and (2) the patients and their families are informed and signed the informed consent. Exclusion criteria: (1) patients with severe heart, liver, kidney, and other vital organ insufficiency; (2) patients with severe diseases of other systems or those who cannot cooperate; and (3) patients who have undergone major surgery recently. This study was carried out after being approved by the Ethics Committee of our hospital.

The patients who were diagnosed with obesity in the outpatient department of our hospital from January 2020 to December 2021 were selected as the research objects. Two patients with severe heart disease and 23 patients with secondary obesity were excluded, and a total of 80 patients were included in the study. The screening criteria are shown in Figure 1. Aged 48-61 years old, 45 males and 35 females were randomly divided into the control group and the intervention group according to the digital table method. All studies used the same method for data collection for easy comparison. There was no significant difference in gender, age, and other data among the participants (P > 0.05) (Table 1 for general information).

Figure 1

Screening and enrolment of patients.

Table 1

General data of the patients (x ± s).

	Lifestyle intervention alone group	Dapagliflozin lifestyle intervention group	t/χ2	P
Female sex (case number (%))	15 (37.5)	20 (50)	5.7	0.20
Age (years)	53 ± 4.4	57 ± 2.9	2.3	0.35
Stature (cm)	162 ± 4.3	166 ± 4.7	10.4	0.12
Weight (kg)	73 ± 4.3	76 ± 2.6	8.3	0.24
Disease course (year)	2.5 ± 1.2	3.3 ± 0.8	5.2	0.09
SBP (mmHg)	106.0 ± 10.2	112.5 ± 14.4	14.2	0.18
DBP (mmHg)	89.3 ± 6.0	95.3 ± 4.9	13.8	0.68
BMI (kg/m2)	27.2 ± 4.6	28.4 ± 2.2	0.2	0.38

2.2. Experimental Method

Treatment methods: the control group was given lifestyle intervention, including nutrition intervention and exercise intervention. Nutritional intervention [16]: (1) during the treatment transition period, the total heat energy is gradually reduced to the predetermined target by 418-836 kJ/d (100-200 kcal/d) per week, usually for 1 month; (2) during the treatment phase, the total calories are determined based on age, gender, height, and disease severity. The average calorie intake of patients was 5852-7524 kJ/d (1400-1800 kcal/d); (3) in the later stage of treatment, it increased by 418 kJ/d (100 kcal/d) every two weeks. Breakfast, lunch, and dinner account for 25%, 40%, and 35% of total caloric energy, respectively. High protein, moderate fat, and carbohydrates were used as dietary intervention models. Carbohydrates, protein, and fat make up 45%-50%, 20%-25%, and 25%-30% of total calories, respectively. Exercise intervention: refer to the “International Conference on Obesity and Physical Activity [17]” to agree on the appropriate physical activity standards. Patients participate in 30-60 minutes of moderate-intensity physical activity every day and reduce static activities and increase activities or recreational activities in daily life. These activities include games, dance, and rhythmic gymnastics and many more forms of exercise. The intervention group was given dapagliflozin 100 mg per day orally on the basis of lifestyle intervention [18].

Waist circumference, body weight, and blood lipids (TG, TC, LDL, and HDL) were measured before and after treatment. Height and weight were measured twice within 0.5 cm and averaged to derive BMI. The Revised Anxiety and Depression Scale (RCADS) questionnaire was completed, which produced scores for total anxiety and depression using the RCADS electronic scoring scheme [19]. The following subscales were included: 1: separation anxiety disorder; 2: generalized anxiety disorder; 3: panic disorder; 4: obsessive-compulsive disorder; 5: major depressive disorder. Questionnaires were completed by patients at baseline and again three months later.

2.3. Statistical Method

Use SPSS 22.0 software for statistical analysis of the data. Normally distributed measurement data is represented by , and nonnormally distributed measurement data is represented by M (1/4, 3/4). The independent sample t-test and Mann–Whitney U test are used for comparison between groups. The count data use case (%) indicates that the χ2 test is used for comparison between groups.

3. Results

3.1. Comparison of LDL, HDL, TC, and TG Levels before and after Treatment

Before treatment, there was no statistical difference in serum LDL, HDL, TC, and TG levels between the two groups (P > 0.05). After 3 months of treatment, compared with the control group, the curative effect of the intervention group was significantly higher than that of the control group; LDL (2.8 ± 3.7 vs. 3.0 ± 3.1, t = 0.6), TC (4.2 ± 0.9 vs. 5.6 ± 1.4, t = 6.5), and TG (1.5 ± 0.6 vs. 1.8 ± 0.6, t = 0.8) levels were significantly decreased; and HDL levels were significantly increased (1.6 ± 0.4 vs. 1.3 ± 0.3, t = 1.1) (P < 0.05) (Table 2).

Table 2

Comparison of blood lipid levels before and after treatment in the two groups (x ± s).

	LDL (mmol/L)		HDL (mmol/L)		TC (mmol/L)		TG (mmol/L)
Group	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment
Lifestyle intervention alone group	3.2 ± 0.8	3.0 ± 3.1	1.1 ± 0.0	1.3 ± 0.3	6.6 ± 3.8	5.6 ± 1.4	1.9 ± 1.6	1.8 ± 0.6
Dapagliflozin lifestyle intervention group	3.3 ± 0.5	2.8 ± 3.7	1.0 ± 0.2	1.6 ± 0.4	6.7 ± 2.2	4.2 ± 0.9	1.8 ± 1.4	1.5 ± 0.6
t	0.6	0.6	0.2	1.1	1.7	6.5	0.7	0.8
P	0.26	0.02	0.18	0.01	0.32	0.00	0.60	0.04

3.2. Comparison of Body Weight and BMI Level of Patients before and after Treatment

There was no significant difference in body weight and BMI level between the two groups before treatment (P > 0.05). After 3 months of treatment, compared with the control group, the weight (58.5 ± 4.6 vs. 67.3 ± 2.2, t = 24.2), BMI (25.7 ± 3.2 vs. 26.7 ± 2.3, t = 2.8), and waist circumference (75.5 ± 6.2 vs. 87.6 ± 4.6, t = 21.2) decreased significantly higher than that of the control group, and the weight loss of the intervention group was statistically significant compared with the control group (P < 0.05) (Table 3).

Table 3

Comparison of body weight and BMI level before and after treatment in the two groups (x ± s).

	Weight (kg)		BMI (kg/m2)		Waistline (cm)
Group	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Loss of weight (%)
Lifestyle intervention alone group	73 ± 4.3	67.3 ± 2.2	27.2 ± 4.6	26.7 ± 2.3	92.4 ± 5.4	87.6 ± 4.6	6.3
Dapagliflozin lifestyle intervention group	76 ± 2.6	58.5 ± 4.6	28.4 ± 2.2	25.7 ± 3.2	89.0 ± 7.3	75.5 ± 6.2	8.2
t	8.3	24.2	0.2	2.8	5.4	21.2	3.2
P	0.25	0.01	0.38	0.04	0.08	0.00	0.01

3.3. Psychometric Results of Patients before and after Treatment

The patients completed the RCADS questionnaire before and after treatment. The average scores were calculated, and the results showed that all scales and total scores in the control group and the intervention group decreased after treatment compared with before treatment. Before the start of treatment, the scores of the patients on the anxiety and depression scale had significant clinical significance (T score > 70), 9 patients with anxiety, accounting for 11.2% of the total, and 6 patients with depression, accounting for 8% of the total. After the intervention, all patient indicators fell below standard values. The anxiety and depression scale (95% CI: 0.2, 16.4; P < 0.05) and the separation anxiety scale (95% CI: 0.4, 20.0; P < 0.05) before and after the intervention were statistically significant.

4. Discussion

With the improvement of living standard in recent years, the incidence of obesity in middle-aged and elderly people has increased significantly [20, 21]. Obesity is highly correlated with blood lipid level, so improving blood lipid level has become a routine treatment plan for middle-aged and elderly obese patients [22, 23]. LDL, TC, TG, and HDL are commonly used clinical blood lipid indicators, among which the increase of LDL is highly correlated with obesity [23, 24]. Other studies have shown that TC and TG can be used as independent risk factors for metabolic diseases such as obesity and may be used as indicators for early prediction of obesity in middle-aged and elderly people [25, 26]. New study shows that HDL levels are inversely related to the incidence of cardiovascular events caused by obesity [23, 27]. The results of this study also showed that HDL in the intervention group was significantly higher than that in the control group.

In this study, 80 middle-aged and elderly obese patients were given basic life intervention and routine nursing. In addition, the intervention group was treated with dapagliflozin. Dapagliflozin is a commonly used hypoglycemic drug in clinic. The latest research shows that dapagliflozin can reduce plasma cholesterol level and lipoprotein level and reduce the production of low-density lipoprotein [28, 29]. Studies have shown that both dapagliflozin and life intervention therapy alone can effectively reduce blood lipid levels in obese patients [30, 31]. The results of this study show that the combined application of life intervention and dapagliflozin can effectively reduce the levels of LDL, TC, and TG in patients, which is consistent with the above studies. And the results of this study show that the combined application of the above two treatment regimens can effectively reduce the body weight, waist circumference, and BMI indicators in middle-aged and elderly obese patients, and these indicators have a hinting effect on the occurrence of metabolic diseases in the middle-aged and elderly.

The advantages of this study include the use of the numerical table method for random allocation to reduce the intragroup differences of the data and the large number of samples to reduce the random error of the experimental results. However, this study also has certain limitations. It is mainly reflected in the fact that the intervention group in this study simply introduced dapagliflozin drug treatment, but no corresponding drug treatment reference was given to the control group, so we can only draw the conclusion that the life intervention combined with dapagliflozin treatment plan is better than the life intervention plan alone.

5. Conclusions

Dapagliflozin in combination with a lifestyle intervention effectively and safely treats excess weight in middle-aged and older adults, reverses obesity-related markers, and improves psychological symptoms. Its curative effect is better than that of using lifestyle intervention alone.