Weight management in T2D

Weight control is an important aspect of preventing or managing type 2 diabetes (T2D). Being overweight or obese is a major risk factor for developing T2D. Maintaining a healthy weight through a combination of diet, lifestyle factors and medication can help prevent, delay or improve T2D. Losing weight can lower the body's resistance to insulin, allowing for better blood sugar control. This can lead to a decrease in the need for diabetes medication or even the ability to stop taking medication altogether. Additionally, weight loss can improve overall health and reduce the risk of complications related to diabetes.

Weight control in T2

Prevalence of obesity in T2D

Obesity has been recognised by the American Medical Association (AMA) and the European Commission as a noncommunicable disease with several pathophysiological aspects, including diabetes^1,2. Obesity has nearly tripled worldwide in all age groups since 1975, including in children, adolescents and young adults³.

Obesity is much more common in children, adolescents and young adults with T2D than in older adults (> 80% vs 56%, respectively)⁴

Due to an increase in the prevalence of obesity in those yet to reach adulthood, T2D has become a concern in children and adolescents.

High BMI increases the risk of T2D

For both men and women, body mass index (BMI) is one of the leading risk factors for disability-adjusted life years (DALYs) of early-onset T2D globally in 2019 (Figure 1)⁵. It was estimated that the number of global deaths and DALYs attributable to a high BMI had more than doubled from 1990–2017⁶.

An increase in both BMI and glycated haemoglobin (HbA1c) levels also increased the risk of developing diabetes from prediabetes⁷

Figure 1. High body mass index is the top risk factor globally (top) and classified by gender (bottom) attributable to T2D burden (Adapted⁵).
DALY, disability-adjusted life year.

Obesity and T2D progression

Obesity is an important driver for the development of beta cell dysfunction, as defined by hyperinsulinemia and impaired glucose-stimulated insulin secretion, and the progression of T2D as illustrated in Figure 2⁸. Because excess fat worsens diabetes, losing weight can remarkably improve the condition.

Figure 2. Obesity is a key contributing factor to the progression of T2D⁸.
ER, endoplasmic reticulum; GSIS, glucose-stimulated insulin secretion.

Lifestyle factors for T2D prevention

T2D is preventable through lifestyle changes, such as weight loss through diet changes that adhere to current recommendations for fat quality, fibre intake, increased use of wholegrain products, fruit and vegetables, and increased physical activity⁹.

The degree of long-term weight loss and adherence to lifestyle changes is directly relevant to T2D risk reduction, and this preventive effect has been shown to last for many years after active intervention⁹

A pooled analysis of the European Diabetes Prevention Study adds to the evidence for T2D prevention through lifestyle changes. Participants who lost 5% of their body weight in one year had a 65% lower incidence of T2D, and maintaining a 5% weight loss for two and three years further decreased the risk of T2D¹⁰.

Current guidelines for the prevention of T2D in people at high risk are based on achieving moderate weight loss (5–10% weight loss) via dietary change and increasing physical activity

Figure 3 shows the current dietary strategies to improve the condition of T2D^11,12.

Figure 3. Dietary strategies are shown to improve (purple) or provide some evidence of improvement (blue) and potential for improvement (orange) in T2D¹³.
IFG, impaired fasting glucose; IGT, impaired glucose tolerance; TDR, total diet replacement; VLED, very low energy diet (< 800 kcal/day).

The Finnish National Diabetes Prevention Program¹⁴ of weight reduction, healthy diet and physical activity for a year included 10,149 people at high risk of T2D (average BMI > 30 kg/m²). Among the 2,730 participants who completed the intervention (median follow-up, 7.4 years), those who lost 2.5–4.9% weight and ≥ 5% weight had a 37% and 29% lower incidence of T2D respectively, than those who did not lose weight.

Keeping weight stable in adulthood is linked to a lower risk of developing diabetes; whole-population weight maintenance strategies have the potential to prevent the disease¹⁵

In a participant-level evaluation of the Centers for Disease Control and Prevention (CDC) National Diabetes Prevention Program (NDPP)¹⁶, the lifestyle change program is one of the key components that provides:

• A trained lifestyle coach – assists participants in learning new skills, encourages them to set and achieve goals and keeps them motivated. The coach will also facilitate discussions and contribute to making the programme enjoyable and engaging
• A CDC-approved curriculum – with lessons, handouts and other resources to help participants make healthy changes
• Group support over a year – a support group of people with similar goals and challenges

Participants in CDC-recognised lifestyle change programmes who lost 5–7% of their body weight and added 150 minutes of exercise per week reduced their risk of developing T2D by up to 58%. Even a decade later, programme participants were one-third less likely to develop T2D than non-participants.

The NDPP programme can also reduce the chances of having a heart attack or stroke, improve health and even reverse a prediabetes diagnosis¹⁴

Lifestyle factors for T2D remission

If obese/overweight people with T2D are able to substantially decrease their body weight, a significant proportion can become non-diabetic. According to a population-based study conducted in Europe, losing 10% or more of one's body weight in the first year after a T2D diagnosis increased the chance of remission by double¹⁷.

Remission was also demonstrated in the DiRECT trial¹⁸, which included 306 patients with T2D from the United Kingdom. For 3–5 months, half of all meals were replaced with a nutritionally balanced liquid diet (825–853 kcal/day):

• At 12 months, the intervention group's mean weight had decreased by 10%, and 46% of the participants had achieved diabetic remission
• At 24 months, the intervention group's average weight loss was 7.6%, and 36% of participants obtained diabetic remission

Post hoc analysis of the DiRECT trial¹⁸ revealed that 24% of participants maintained a 10 kg weight loss, and 64% remained in remission. At 8 years, approximately 50% of intensive lifestyle intervention participants lost and maintained 5% of their initial body weight, while 27% lost and maintained 10%.

Additional weight loss benefits in people with T2D are documented by secondary analyses of the Look AHEAD trial and other significant cardiovascular outcome studies, including better mobility, physical and sexual function, and health-related quality of life (QoL)¹⁹. Additionally, certain subgroups, such as those who lost more than 10% of their body weight and those with moderately or poorly controlled diabetes (HbA1C > 6.8% at baseline), had better cardiovascular outcomes¹⁹.

The magnitude of weight loss, regardless of diet (as long as it is sustainable), is the most important factor in achieving diabetes remission^13,18

If lifestyle interventions alone are insufficient to achieve weight loss, pharmacological and surgical treatments may be considered.

Communication is essential

Patient-centred communication has been linked to better disease knowledge, self-care, QoL and metabolic control in T2D^20-22

Consistent with this evidence, leading organisations, such as the American Diabetes Association (ADA)²³ and the International Diabetes Federation (IDF)²⁴, are currently advocating for patient-centred communication in diabetes management.

The ADA's current clinical practice recommendations state that a person-centred communication style using inclusive, non-judgmental language and active listening to elicit individual preferences and beliefs and assess potential barriers to care should be used to optimise health outcomes and health-related QoL. The ADA encourages the use of person-centred, non-judgmental language that fosters collaboration between individuals and healthcare professionals (HCPs), including person-first language (e.g., ‘person with obesity’ rather than ‘obese person’)¹⁹.

It is critical for HCPs to develop professional communication skills and a fundamental mindset based on a person-centred approach before introducing specific techniques and tools²⁵. Some of the constraining and facilitating factors experienced by participants during clinical encounter communications include²⁶:

• Power imbalance vs partnership in decision making in the patient-provider relationship
• Socioeconomic factors, health literacy, responsibility related to disease and treatment
• Quality of communication and consistency in providing information

In the UK, a Language Matters Working Group has been set up by NHS England to improve awareness of the impact words may have on the care of people living with diabetes (Table 1)²⁷.

Table 1. NHS recommendations for improving communication with people with diabetes²⁷.

Pharmacological weight loss strategies for T2D

Professor Caroline Apovian gives an overview of the pharmacological weight loss strategies for type 2 diabetes (T2D) in the video below.

Pharmacological weight loss strategies for T2D

Treatment considerations for weight loss in T2D

Healthcare professionals (HCPs) should take into account each medication's impact on weight when planning treatment programmes because there are various effective treatments available. Below are the American Diabetes Association’s (ADA) recommendations in obesity and weight management for the prevention of T2D¹⁹:

• When choosing glucose-lowering medications for people with type 2 diabetes who are overweight or obese, consider the medication’s effect on weight
• Whenever possible, minimise medications for comorbid conditions that are associated with weight gain
• Obesity pharmacotherapy is effective as an adjunct to nutrition, physical activity and behavioural counselling for selected people with type 2 diabetes and a BMI ≥27 kg/m²; potential benefits and risks must be considered
• If obesity pharmacotherapy is effective (typically defined as ≥5% weight loss after 3 months’ use), further weight loss is likely with continued use
• When early response is insufficient (typically < 5% weight loss after 3 months’ use) or if there are significant safety or tolerability issues, consider discontinuation of the medication and evaluate alternative medications or treatment approaches

In the following video, Professor Caroline Apovian summarises clinical guideline recommendations when considering individual patient characteristics.

Clinical guideline recommendations based on individual patient characteristics

Medication that both encourages weight loss and lowers glucose levels is preferred when greater weight loss is the main therapeutic goal. In addition to managing hyperglycaemia, metformin is frequently used to promote moderate weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist therapies promote weight loss¹⁹. Figure 4 summarises the weight loss for the most commonly used diabetes medications. Real-world evidence shows that treatments of metformin plus sodium–glucose cotransporter-2 inhibitors (SGLT2i; 2.4%), SGLT2i (1.7%), and GLP-1 RA (1.6%) resulted in a greater reduction in body weight values than other antidiabetic groups²⁸.

Figure 4. Overview of weight loss with commonly used antidiabetic medication²⁹.

Primary Care Diabetes Europe treatment recommendations³⁰ for patients with obesity are as follows:

• Consider initiating metformin plus GLP-1 RA/SGLT2i rather than stepwise
• Metformin as first-line therapy
• GLP-1 RA or SGLT2i as second-line therapy
• Where possible, avoid treatments that cause weight gain, including most sulfonylureas, glinides, pioglitazone and insulin
• If basal insulin is required, consider fixed-ratio insulin/GLP-1 RA combinations, if available

A joint consensus report by the ADA and the European Association for the Study of Diabetes (EASD) on the management of hyperglycaemia in T2D states that weight reduction is a targeted intervention for managing T2D³¹

Figure 5 provides a schematic approach for the achievement and maintenance of glycaemia and weight management³¹.

Figure 5. Use of glucose-lowering medications in the management of obesity in T2D³¹.
CGM, continuous glucose monitoring; DPP-4i, dipeptidyl peptidase-4 inhibitors; DSMES, diabetes self-management education and support; GLP-1 RA, glucagon-like peptide-1 receptor agonists; HbA1c, glycated haemoglobin; SDOH, social determinants of health; SGLT2i, sodium–glucose cotransporter-2 inhibitors; TZD, thiazolidinedione.

GLP-1 RA for weight loss in T2D

In the following video Professor Caroline Apovian discusses recent changes to pharmacological weight loss intervention options, including both GLP-1 RAs and SGLT inhibitors.

Pharmacological weight loss interventions and strategies for type 2 diabetes

A meta-analysis of 34 trials comparing GLP-1 RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and taspoglutide) with placebo or another GLP-1 RA in patients with T2D and poor control on oral agents (typically metformin) found that all approved GLP-1 RAs reduced weight compared with placebo, with little difference between individual agents³². In the comparative effectiveness trial (GRADE), treatment with liraglutide was associated with more weight loss (3.5 kg) than sitagliptin (2.0 kg), glimepiride (0.73 kg) or glargine (0.61 kg)³³.

In a comparative effectiveness analysis of seven GLP-1 RAs from 64 trials, dulaglutide ≥ 1.5 mg, exenatide immediate-release (ER) and exenatide extended-release (ER), efpeglenatide, liraglutide ≤ 1.8 mg, liraglutide > 1.8 mg, lixisenatide and semaglutide < 2.4 mg or 2.4 mg subcutaneous (SC), semaglutide oral, and taspoglutide were all associated with significant weight loss when compared to placebo. Semaglutide (SC and oral) and liraglutide were the most effective GLP-1 agents for weight loss after at least 12 weeks of treatment³⁴.

In a large real-world study (N = 2,405; mean age, 43 years; mean BMI, 37 kg/m²), treatment with GLP-1 RA resulted in a mean weight loss of 1.1% 8 weeks after treatment and 2.2% 72 weeks after treatment. About 800 patients had lost ≥ 5% body weight at 72 weeks³⁵.

Results from another real-world study (N = 589; mean age, 54 years; mean BMI, 41.2 kg/m²) suggested that real-world benefits may be lower than those seen in clinical trials: 43.5% of participants had lost ≥ 5% of their body weight but 32.3% had gained weight. Most importantly, 45.2% of the cohort had discontinued the medication within 12 months, and 64.7% had discontinued the medication at 24 months³⁶.

Dual-acting GLP-1 and GIP RA for weight loss in T2D

Dual-acting therapy GLP-1/GIP RA appears to be more effective than GLP-1 RAs alone in terms of weight loss. A recent meta-analysis of seven trials found that tirzepatide was more effective than GLP-1 RAs in reducing body weight; reductions ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg^.37.

DPP-4 inhibitors vs GLP-1 RAs

GLP-1 RAs are generally preferred over dipeptidyl peptidase-4 (DPP-4) inhibitors due to greater HbA1c reductions and clinically significant weight loss observed in clinical trials – a mean weight loss of -0.79 to -6.1 kg was observed with GLP-1 RA and 0.0 to -1.9 kg was observed with sitagliptin. DPP-4 inhibitors have only a minor effect on endogenous GLP-1 levels, resulting in smaller glycaemic reductions with little impact on weight loss³⁸.

SGLT1 and 2 inhibitors

A meta-analysis of 116 trials has shown a mean weight reduction of -1.67 kg with a SGLTi compared with placebo. Combined SGLT1/SGLT2i showed significantly greater weight reduction than SGLT2i alone, with a mean difference of -0.70 kg³⁹.

Combination of GLP-1 RAs and SGLT2 inhibitors

According to a pooled analysis of eight trials, short-term GLP-1 RA/SGLT2i combination therapy may be a better option for inadequately controlled, overweight or obese patients with T2D who are more likely to achieve weight loss goals. The beneficial effects of weight loss are more pronounced than the individual monotherapies but became less significant after 1 year⁴⁰.

Patient involvement in weight management

Professor Caroline Apovian discusses the importance of patient involvement and education in weight management in T2D in the following video.

Patient involvement in weight management

Patient involvement is crucial in weight management for T2D. Here are several ways patients can be involved^41,42:

1. Education: Patients should be educated on the importance of healthy eating habits, portion control and physical activity
2. Goal setting: In consultation with their healthcare professional (HCP), patients can set realistic weight loss goals
3. Healthy eating: Patients can improve their diet by limiting processed foods, sugar and saturated fats, as well as eating a healthy, balanced diet that is low in calories and high in nutrients, such as wholegrains, fruits and vegetables
4. Physical activity: Patients should avoid sedentary behaviour and instead engage in regular physical activity, such as brisk walking, to aid in weight loss and overall health
5. Maintain a healthy weight: Losing 1–2 pounds per week gradually can help with glucose control
6. Collaboration: Patients should collaborate with their HCP to develop a customised weight-management plan
7. Self-monitoring: Patients can track their progress and make adjustments as needed by regularly monitoring their weight and blood sugar levels
8. Medications: Patients can consult with their HCP to see if medication is required to aid in weight management
9. Adherence: Patients should consistently adhere to their exercise, diet plans and medication routine as part of their weight management regimen
10. Support: Patients can seek support from friends, family or support groups to help with weight loss efforts
11. Reflection: Patients should reflect on their progress and make changes to their plans as needed to achieve their goals

By being actively involved in their weight management, patients can greatly improve their chances of successfully managing T2D.

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