Retha Harmse highlights the warnings, risks and how to manage the high cost of semaglutide.

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Semaglutide has gained considerable attention for its effectiveness in managing Type 2 diabetes and promoting weight loss. However, as its popularity has grown, so too have concerns regarding its use, particularly regarding compounded off-brand formulations and the potential risks and side effects of long-term use.

The U.S. Food and Drug Administration (FDA) has issued warnings against the use of compounded semaglutide formulations, emphasising that these versions may not meet the safety and efficacy standards of the original FDA-approved product.

Mechanism of action of semaglutide

Semaglutide belongs to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. This class of medication mimics a hormone naturally produced in the intestines in response to food intake, playing a crucial role in regulating blood glucose levels and appetite. The drug mechanism works by:

1. Stimulating insulin secretion: In response to meals, it enhances insulin release from the pancreas, which helps lower blood glucose by facilitating glucose uptake into cells, especially muscle and fat tissues. This action helps prevent hyperglycaemia (high blood glucose) after eating.
2. Inhibiting glucagon release: Glucagon is a hormone that raises blood glucose by signalling the liver to release stored glucose. Semaglutide reduces glucagon secretion, helping to prevent the liver from producing excessive glucose, especially when blood glucose is already elevated.
3. Slowing gastric emptying: Semaglutide slows the rate at which food leaves the stomach, promoting a feeling of fullness (satiety) and reducing appetite, which is beneficial for weight management in people with Type 2 diabetes.
4. Improving beta cell function: Over time semaglutide improves the function of beta cells in the pancreas, responsible for insulin production, potentially enhancing long-term blood glucose control.

The risks

While semaglutide is effective for managing Type 2 diabetes and aiding weight loss, it does come with potential risks:

1. Gastrointestinal side effects: Common side effects include nausea, vomiting, diarrhoea, and abdominal discomfort. These symptoms are most pronounced when starting the medication and may decrease over time, though some may experience persistent symptoms.
2. Hypoglycaemia: While semaglutide itself doesn’t typically cause low blood glucose, it can increase the risk of hypoglycaemia when used with other diabetes medications, particularly insulin or sulfonylureas. Regular monitoring of blood glucose is important in these cases.
3. Pancreatitis risk: There have been reports of pancreatitis (inflammation of the pancreas) in some users. If symptoms such as severe abdominal pain, nausea, or vomiting occur, immediate medical attention is needed.
4. Thyroid cancer concerns: Animal studies have shown an increased risk of thyroid tumours with GLP-1 receptor agonists. However, human studies haven’t clearly confirmed this risk. Still, semaglutide carries a black box warning for potential thyroid C-cell tumours, and it should be avoided by anyone with a personal or family history of thyroid cancer.
5. Kidney function: Reports have indicated that semaglutide may cause kidney injury, especially in people who experience dehydration due to gastrointestinal side effects. Kidney function should be monitored regularly, particularly in those with existing kidney issues.

Impact on lean mass

One concerning aspect is its effect on body composition. Research has shown that users on high-dose semaglutide or tirzepatide may lose a significant amount of lean mass (about 6,35kg of muscle) along with body fat. This loss of muscle mass represents about 40% of the total weight lost.

While these drugs promote fat loss, the loss of lean mass can have detrimental long-term effects, including decreased metabolism, lower strength, and higher risks of injury. Furthermore, if the drug is stopped, people may experience weight regain, and there’s concern that the muscle mass lost might not be regained, leading to an unfavourable lean-to-fat ratio.

The high cost

The cost is one of the biggest barriers to long-term use. With monthly expenses reaching exorbitant amounts, many users find it difficult to maintain the medication without medical aid or patient assistance. Here are strategies to manage the cost:

1. Explore patient assistance programme: The manufacturer of semaglutide offers patient assistance programmes for those who qualify. It’s worth exploring whether you meet the eligibility criteria for such programmes.
2. Insurance coverage and co -pay assistance: If you have medical aid, check with your medical aid to see if it covers this drug. Some medical aids provide co-pay cards or discounts that can significantly reduce out-of-pocket costs.
3. Consider generic alternatives: While there is no generic version yet, it’s important to keep an eye on future developments. Newer, more affordable GLP-1 receptor agonists may emerge, and discussing these options with your healthcare provider can offer more cost-effective alternatives.
4. Partner with your healthcare provider: If semaglutide becomes financially unfeasible, consult your healthcare provider. They may be able to adjust your treatment plan or recommend other, more affordable therapies that still provide effective diabetes management.

 Sustaining the usage regimen

Semaglutide is typically administered once a week via subcutaneous injection, which can be convenient. However, consistency is key to its effectiveness. To maintain your regimen:

1. Set a routine: Choose a day each week to administer your injection and stick to that schedule.
2. Track progress: Regularly monitor your blood glucose levels, any side effects, and changes in your body. This can help you and your healthcare provider assess your treatment’s effectiveness.
3. Manage side effects: If you experience side effects, like nausea or stomach discomfort, talk to your healthcare provider.
4. Stay engaged with your healthcare provider: Regular check-ins with your doctor are essential to adjust your treatment as necessary.

Alternative lifestyle options

If you find that the cost is unsustainable, or the side effects are too challenging, it may be time to consider alternative lifestyle options. Weight management through healthy eating, regular physical activity, and other non-drug-based interventions can be effective and more affordable ways to manage Type 2 diabetes and promote overall health.

Take away message

Semaglutide can be an effective tool for managing Type 2 diabetes and aiding weight loss, but it comes with potential risks, including the loss of lean mass and high costs.

For those struggling with the expense, exploring financial assistance options, considering alternative medications, and discussing lifestyle changes with a healthcare provider are essential steps to maintaining health without the financial burden.

If semaglutide isn’t sustainable for you, there are various other approaches to diabetes management that may offer long-term success.

Dr Paula Diab gives an overview of GLP-1 drugs, their approved uses, and who might benefit the most. She also explores newer combinations, oral formulations, and clinical trials shaping the future.

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Over the past decade, GLP-1 receptor agonists (GLP-1 RAs) have revolutionised the management of Type 2 diabetes and obesity. These medications, initially developed to improve blood glucose control, have since demonstrated profound benefits for weight loss, cardiovascular health, and even emerging possibilities in treating other metabolic conditions. With their widespread availability and increasing popularity, one key question remains: who should receive GLP-1 drugs?

What are GLP-1 drugs?

GLP-1 receptor agonists mimic the action of a natural hormone called glucagon-like peptide-1 (GLP-1), which is released in response to eating. They regulate blood glucose and appetite by:

• Stimulating insulin secretion.
• Slowing gastric emptying (keeping food in the stomach longer, which helps you feel full).
• Suppressing glucagon, a hormone that raises blood glucose.
• Reducing appetite through signals to the brain. 

GLP-1 drugs available today

There are several GLP-1 receptor agonists available currently (not all on the South African market). Each has its own unique formulations, dosing schedules, and benefits. Here’s a breakdown of the most commonly used medications:

1. Exenatide (Byetta, Bydureon)

• Indication: Type 2 diabetes.
• Form: Byetta, a twice-daily injection, was previously available in SA. Bydureon, the weekly injection isn’t available in SA.

• Highlights: One of the first GLP-1 drugs, effective for blood glucose control but less commonly used today due to newer options with greater weight-loss benefits.

2. Liraglutide (Victoza, Saxenda)

• Indication:
  • Victoza: Type 2 diabetes and cardiovascular risk reduction.
  • Saxenda: Obesity or overweight with comorbid conditions (e.g. hypertension, sleep apnoea).
• Form: Daily injection.
• Availability: Both available and licensed in SA.
• Highlights: A proven option for weight loss and diabetes, though some patients find daily dosing inconvenient.

3. Dulaglutide (Trulicity)

• Indication: Type 2 diabetes and cardiovascular risk reduction.
• Form: Weekly injection.
• Availability: Available and licensed in SA.
• Highlights: Convenient once-weekly dosing, widely used for both blood glucose and heart health benefits.

4. Semaglutide (Ozempic, Wegovy, Rybelsus)

• Indication:
  • Ozempic: Type 2 diabetes and cardiovascular risk reduction.
  • Wegovy: Obesity or overweight with comorbid conditions.
  • Rybelsus: Oral form for Type 2 diabetes.
• Form: Weekly injection (Ozempic and Wegovy) or daily oral tablet (Rybelsus).
• Availability: Only Ozempic is currently available in SA, others may become available later in the year.
• Highlights: Semaglutide has set a new standard for weight loss, with Wegovy often leading to 15% or more body weight reduction in clinical trials.

5. Tirzepatide (Mounjaro)

• Indication: Type 2 diabetes (with anticipated obesity indication approval).
• Form: Weekly injection.
• Availability: Available in SA as of February 2025.
• Highlights: A dual-action drug targeting both GLP-1 and GIP (another gut hormone), delivering remarkable weight loss and glucose control.

Who can benefit from GLP-1 drugs? 

1. People with Type 2 diabetes

For individuals struggling with blood glucose control, GLP-1 drugs offer a highly-effective option. Beyond lowering HbA1c levels, these medications often reduce cardiovascular risks and may even slow the progression of kidney disease in people with diabetes.

2. Individuals living with obesity

Obesity is now recognised as a chronic, multi-factorial disease, not simply a result of willpower. GLP-1 drugs like semaglutide brand 2 and liraglutide brand 2provide a powerful tool for weight loss by addressing the biological mechanisms driving appetite and energy balance.

Eligible patients typically have:

• A body mass index (BMI) ≥ 30 (obesity), or
• A BMI ≥ 27 (overweight) with weight-related health conditions like high blood pressure or Type 2 diabetes.

3. People with cardiovascular risk

Several GLP-1 drugs, including liraglutide, semaglutide, and dulaglutide, have demonstrated benefits in reducing the risk of heart attack, stroke, and cardiovascular death in people with Type 2 diabetes and existing heart disease.

4. Those with prediabetes

Emerging evidence suggests that GLP-1 drugs could help prevent or delay the onset of Type 2 diabetes in individuals with prediabetes by improving insulin sensitivity and promoting weight loss.

5. Individuals facing plateaus with lifestyle changes

For those who have struggled with diet and exercise alone, GLP-1 drugs can offer an additional boost. These medications complement healthy lifestyle choices and provide sustainable weight-loss results.

New combinations and oral GLP-1 options

The field of GLP-1 therapies is rapidly evolving, with exciting developments that enhance convenience and efficacy.

Combination therapies

• Tirzepatide: Combines GLP-1 and GIP receptor agonism for dual-action benefits.
• Next-generation therapies: Ongoing trials are exploring triple-action drugs targeting GLP-1, GIP, and glucagon receptors, potentially amplifying weight-loss effects.

Oral formulations

• Oral semaglutide: The first and only oral GLP-1 drug, offering an alternative for patients who prefer not to use injections.
• Future options: Researchers are investigating improved oral formulations to increase bioavailability and effectiveness.

Current clinical trials and future directions

Several clinical trials are expanding the potential uses of GLP-1 drugs. Studies, such as STEP and SURMOUNT, are investigating the weight loss potential in non-diabetic populations. Other studies are looking into the use of GLP1 medications to reduce liver fat and treat liver disease associated with diabetes and obesity.

Certainly, there is also great interest in looking into the cardiovascular benefits of GLP1 medications not only in diabetic populations but also in people without diabetes who exhibit risk factors for cardiovascular disease.

Finally, early research suggests GLP-1 drugs might also have protective effects in diseases like Alzheimer’s and Parkinson’s, but further investigation is required.

Are GLP-1 drugs right for you?

 Not everyone is a candidate for GLP-1 drugs. These medications are generally reserved for people who:

• Have Type 2 diabetes or obesity.
• Are unable to achieve sufficient results with lifestyle changes alone.
• Have no contraindications, such as a history of medullary thyroid cancer or pancreatitis.

It’s also important to consider cost. While some medical aid plans cover GLP-1 drugs, others may not, particularly for obesity treatment. Speak to your doctor to determine your eligibility and explore various options that may be available.

Overview

GLP-1 receptor agonists are reshaping how we approach Type 2 diabetes and obesity, offering hope to millions worldwide. From improved blood glucose control to life-changing weight loss, these medications address the biological underpinnings of chronic conditions that were once considered unsolvable.

If you are interested in knowing more or think that these drugs might be right for you, please consult your doctor. Together, you can explore your health goals, treatment options, and the exciting possibilities these ground-breaking medications provide.

Diabetes breakthroughs

This year Dr Paula Diab will present a series of articles that address various new breakthroughs in diabetes management. These will focus mainly on medications that are becoming available – different ways of using old medications, new formulations, and new drugs in the pipeline.

– OTHER INTERESTING READS –

Monique Marais and Marionette Roselt outline the importance of wound care management in the diabetes community.

Listen to this article below or wherever you get your podcasts or visit our playlist.

People living with diabetes are more prone to wounds and/or chronic wounds due to several factors that affect the body’s ability to heal.

Neuropathy (nerve damage) can cause a loss of sensation, especially in the feet and lower legs, making it difficult to detect injuries like cuts or blisters, which can worsen over time without treatment.

Poor circulation (peripheral artery disease (PAD)) caused by narrowed blood vessels, reduces blood flow to the extremities, slowing the delivery of oxygen and nutrients needed for healing.

High blood glucose levels (hyperglycaemia) can damage blood vessels, weaken the immune system, and interfere with collagen production, making it easier for infections to develop and harder for wounds to heal.

Additionally, a weakened immune response further increases the risk of infections, such as cellulitis or gangrene, as the body’s ability to fight bacteria is compromised.

People who have diabetes also have thicker, less elastic skin, which is more prone to cracking and injury, and they produce less collagen, which is crucial for tissue repair.

Furthermore, increased pressure and poor foot care habits, often due to neuropathy and improper footwear, can lead to pressure sores and ulcers. All these factors combined make wound prevention and proper skin care essential for people with diabetes.

As a result of people living with diabetes being more prone to wounds, it’s important to know the various types of wounds that can develop to prevent them from developing.

The most common types of wounds

1. Diabetic foot ulcers (DFUs)

• Most common type of wound for people living with diabetes.
• Occurs due to neuropathy, which leads to a lack of sensation in the feet, and peripheral artery disease (PAD), which reduces blood flow, slowing healing.
• Common triggers: pressure from shoes, minor cuts, blisters, or unnoticed injuries.
• Can lead to infection and in severe cases amputation.

2. Pressure ulcers (bedsores)

• People living with diabetes who have limited mobility are at risk of pressure injuries, especially on bony areas like heels, ankles, hips, and the sacrum.
• Caused by prolonged pressure, friction, moisture, or shear forces.

3. Venous stasis ulcers

• Occurs when poor circulation leads to blood pooling in the legs, resulting in swelling and ulcer formation.
• Typically found on the lower legs and ankles.

4. Arterial ulcers

• Result from peripheral artery disease (PAD).
• Appears as deep, painful wounds, often with a punched-out appearance, typically on the feet, toes, or lower legs.

5. Surgical wounds and poor healing

• People with diabetes have delayed wound healing due to impaired blood flow and immune response.
• Surgical incisions take longer to heal and are at higher risk of infection or non-union (not healing at all).

6. Traumatic wounds (cuts, burns, scrapes)

• Minor injuries can escalate quickly due to poor healing capacity and susceptibility to infection.
• Common causes: household accidents, shoe-related friction, or stepping on sharp objects.

7. Infections (abscesses, cellulitis, gangrene)

• Even small wounds can become infected quickly, leading to serious conditions, such as cellulitis (skin infection) or gangrene (tissue death).

Prevention action tips

People living with diabetes can take several preventative actions to avoid wounds and manage them effectively if they occur.

• Regular foot care is crucial — checking feet daily for cuts, blisters, redness, or swelling, and moisturising to prevent dry, cracked skin. Ensure you dry between your toes after washing or swimming.
• Wearing proper footwear that fits well and provides support can help reduce pressure points and prevent injuries. Inspect shoes on the inside to ensure no foreign objects are in the shoe that can contribute to pressure injuries or lacerations.
• Keeping blood glucose levels under control is essential to promote better circulation and faster healing.
• Practising good hygiene by keeping the feet clean and dry helps prevent infections.
• Regular medical check-ups with a healthcare provider or podiatrist can catch potential issues early.
• Engaging in gentle exercise improves circulation, while avoiding smoking and excessive alcohol consumption can further support vascular health.

If a wound does occur, it should be treated promptly by cleaning it, applying appropriate dressings, and seeking medical attention if it doesn’t heal or shows signs of infection.

Basic wound care at home

It’s always best to consult with a GP or wound care practitioner that has professional opinions and guidelines before attempting to do the wound care yourself.

Basic principles to follow on minor cuts or wounds at home:

• Wash your hands thoroughly before touching the wound.
• Clean the wound immediately with warm water and a disinfectant.
• If the wound is large or deep, consider using a sterile saline solution or clean water to flush out any debris or foreign objects. This helps create a clean environment for healing. Consult with a professional if there is excessive bleeding or pain.
• Avoid ointments that can cause irritation or allergic reactions.
• Cover the wound to keep it clean and dry.
• Monitor for signs of infection (see below) and seek professional care if it becomes infected or the wound healing process is prolonged.
• Manage your blood glucose levels to promote wound healing.
• Maintain good circulation to promote wound healing

Recognising the signs of infection

• Warmth around the wound: If the skin around the wound feels hot to the touch, it could mean the body’s immune system is fighting the infection.
• Increased redness and swelling: If the area around the wound become more red, swollen, or warm, it could indicate an infection is developing.
• Increased pain: Some pain is normal, but persistent or worsening pain around the wound could be a sign of infection.
• Pus or drainage: The presence of thick, yellow, green, or foul-smelling discharge is a clear sign of infection. Clear fluid is usually normal, but anything cloudy or discoloured is concerning, as well as if there is an increase in exudate levels.
• Bad odour from the wound: An unusual or foul smell coming from the wound is often a sign of bacterial infection.
• Increased drainage or bleeding: A sudden increase in fluid coming from the wound, especially if it’s thick or bloody, can be a warning sign.
• Fever or chills: A fever (over 38°C) or feeling generally unwell with chills can indicate the infection is spreading beyond the wound. Seek urgent medical attention if these symptoms appear.
• Delayed healing: If the wound isn’t improving or appears to be getting worse after a few days, it may be infected and require medical attention.
• Skin discolouration: If the skin around the wound turns dark, bluish, or black, it could indicate serious tissue damage or a spreading infection.
• Swollen lymph nodes: Tender lumps under the arms, neck, or groin may signal that the body is fighting an infection.

Wound dressing and treatment options

It’s important to educate yourself on the types of wound dressing and treatment options available so that you can discuss it with your GP or wound care practitioner and decide on an appropriate treatment plan.

The below guidelines serve as options for wound care treatment. Keep in mind that this is a field of expertise that is constantly evolving and improving, and what works now might not be the best treatment plan in the future.

Wound care dressing types

When choosing the right dressings for diabetic wound care, several factors should be taken into consideration:

Taking ownership of your health is crucial for anyone living with diabetes to achieve better outcomes and lead healthier lives. By actively managing your condition through regular monitoring, healthy lifestyle choices, and adherence to medical advice, you can prevent complications and improve your quality of life.

Equally important is the role of healthcare professionals in providing education, support, and personalised care to empower you in this journey. A collaborative effort between you and healthcare providers is essential to ensure effective diabetes management, early intervention, and overall well-being. Together, through awareness, commitment, and proactive care, better health outcomes this can be achieved for those living with diabetes.

References

1. How wounds heal: MedlinePlus Medical Encyclopaedia
2. Evaluation and Treatment of Diabetic Foot Ulcers | Clinical Diabetes | American Diabetes Association
3. Diabetic Foot Ulcers: Causes and Treatments
4. Diabetic Wound Care: Why These Wounds Take Longer to Heal and What You Should Know About Treatment – R3 Wound Care & Hyperbarics
5. South Africa – International Diabetes Federation
6. UP EXPERT OPINION: South Africa has more than 4 million people living with diabetes – many aren’t getting proper treatment | University of Pretoria
7. 2023-11 – Diabetes – SA’s second biggest killer – Wits University
8. Assessment of prevalence and risk factors of diabetes and pre-diabetes in South Africa | Journal of Health, Population and Nutrition | Full Text
9. South Africa diabetes report 2000 — 2045
10. A Complete Guide for Wound Care for Diabetics?
11. Diabetes and Wound Care, Steps to Find Healing | Banner Health
12. The Dos and Don’ts of Diabetic Wound Care: Midwest Institute for Non-Surgical Therapy: Vascular and Interventional Radiologists

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Lynette Lacock discusses how venous disease is linked to diabetes and how to prevent future complications.

Listen to this article below or wherever you get your podcasts or visit our playlist.

What is venous disease?

Venous disease is any condition that affects the veins in your body. Veins are flexible, hollow tubes that are part of the circulatory system that moves blood through your body. The different types include: blood clots, deep vein thrombosis (DVT), superficial thrombophlebitis, chronic venous insufficiency, varicose and spider veins, venous ulcers, and arteriovenous fistulas.

Unfortunately, these conditions are familiar complications to millions of people who have unmanaged diabetes. The vascular system is negatively impacted by diabetes when it’s uncontrolled. This can result in poor circulation, deep vein thrombosis or clots, venous stasis, and varicose veins particularly in legs.

Why are people with diabetes susceptible to varicose veins?

You may have seen someone with varicose veins. They appear as lumps near the surface of the skin with a darker or bluish colour. This is actually enlarged vein walls that have become weakened over time due to the inability to push the blood back up toward the heart. This is caused by poor circulation and malfunctioning valves in the veins. Besides its distinctive appearance, it can be very uncomfortable, resulting in heavy aching legs and possible ulceration.

In diabetes, the risk of developing varicose veins is heightened for several reasons:

• Altered circulation: Over time, uncontrolled high blood glucose can damage the blood vessels. As the vessels become worse, the valves start to malfunction due to the increase venous pressure leading to stretching of the veins causing them to become varicose.
• Overweight and inactive lifestyle: Did you know that when you walk, your leg muscles help the blood defy gravity and pump it back up toward your heart?

 Unfortunately, the reverse is also true, inactivity helps gravity keep the blood in your lower extremities. Excessive weight puts pressure on the venous system making it harder to circulate the blood which compounds the problem.

• Altered sensation due to neuropathy: Due to the decrease in sensation when you have peripheral neuropathy, you may be unaware that your legs are tight and sore. Therefore, you may not realise you have a problem until you start seeing the varicose veins or other problems appear.

Venous insufficiency in those with diabetes

When the venous system continues to malfunction, it’s called venous insufficiency. When the valves in the veins are damaged the condition becomes chronic. Chronic venous insufficiency can cause complications, such as swelling of the lower extremities and venous ulcers. Once ulcers appear, there is an increased risk of infection.

• Delayed wound healing: Due to compromised circulation in people with diabetes, injuries and wounds will take longer to heal and are more prone to infection because of the delay in healing.
• Chronic increased venous pressure: Obesity and a sedentary lifestyle can make circulation worse. Venous stasis can lead to complications because it starts to damage tissue in the area.
• Complications of diabetic neuropathy: Having peripheral neuropathies makes it difficult to feel when something isn’t right. This delay in addressing a problem early can lead to complications that require a longer treatment.
• Immune system weaker: Spikes in blood glucose or uncontrolled blood glucose can have negative effects on your immune system making it harder for the body to fight off infections. Having varicose veins only makes it harder to fight off infections due to venous stagnation.

What is a deep vein thrombosis?

A deep vein thrombosis (DVT) is a clot deep in the vein that can become a life-threatening condition if the clot travels to the lungs causing a pulmonary embolism (PE). Therefore, it’s essential to be aware of the symptoms to seek early treatment.

The symptoms include a warm, red, swollen and painful extremity.  Should you develop any of these symptoms, you should see your healthcare provider immediately.

People living with diabetes have an increased risk of DVT due to the following reasons.

1. Increase in thickness of blood: Higher blood glucose levels can make blood more viscous and increase clotting factors, leading to an increased risk of clot formation.
2. Obesity and inactive lifestyle: Obesity and diabetes slow down the circulation in the lower extremities. This greatly increases the risk of developing a DVT.
3. Chronic systemic inflammation: Chronic inflammation is often present in people with diabetes due to prolonged high blood glucose levels and insulin resistance. This inflammation can damage blood vessel walls and increase the risk of clot formation.
4. Vascular cellular damage: When the blood glucose spikes or remains elevated the endothelial lining of the vessels gets damaged. This damage produces inflammation in the vessels making the chance of a clot formation higher.

How to prevent venous disease if you have diabetes?

There are measures you can take to prevent early onset or the severity of venous disease.

1. Stable blood glucose: Unstable and fluctuating blood glucose can cause inflammation and damage to your vessels and decrease circulation. Therefore, you must maintain a stable blood glucose level by taking your medications, eating correctly, and checking your blood glucose regularly.
2. Maintain a healthy weight: Exercise and follow a healthy diet to maintain an optimal weight and prevent inflammation and added pressure on leg veins.
3. Compression stockings: Compression stockings can help prevent blood from pooling in the lower extremities which can prevent a DVT. Discuss using stockings with your healthcare provider. You may need to be fitted for these stockings or you may not be a candidate for stockings if you have peripheral neuropathy.
4. Keep fit and active: Maintaining physical fitness can go a long way in preventing the development and progression of venous disease. Speak to your healthcare provider about which exercises are best for you. Keeping your leg muscles fit and strong will help push the blood back to your heart preventing venous stasis.
5. Avoid inactivity: Don’t stand or sit for long periods at a time as this will cause swelling and pressure in the legs. Changing positions often, elevating your legs, and lower leg exercises can prevent venous stasis.
6. Foot-, wound- and skin- care routine: Examine your skin for cracks or ulcers and signs of varicose veins regularly. See a podiatrist every six months to have your nails trimmed and feet examined. See your healthcare provider with any signs of infection or DVT as soon as possible to prevent complications.

References

1. usaveinclinics.com
2. veinspecialists.com
3. pmc.ncbi.nlm.nih.gov
4. https://veincenter.doctor/chronic-venous-insufficiency-diabetes-mellitus/

Dr Louise Johnson explains the new guidelines for managing early Type 1 diabetes.

Listen to this article below or wherever you get your podcasts or visit our playlist.

Type 1 diabetes 101

Type 1 diabetes is an autoimmune condition that occurs as a result of destruction of the beta cells of the pancreas. The beta cells produce insulin in normal healthy people. This destruction leads to sever insulin deficiency. Without insulin treatment, this will lead to diabetic ketoacidosis and death. Thus, lifelong insulin therapy is needed for survival. Type 1 diabetes represent 5–10% of all diabetes. The diagnosis classically occurs in children and adolescents but can also occur in adulthood.

Classically Type 1 diabetes present over the course of days or weeks in children and adolescents with drinking a large amount of water and passing a large amount of urine. This is associated with weight loss, dry mouth, and blurred vision. These are all symptoms of high blood glucose and is associated with or without ketones.

Four antibodies that cause Type 1 diabetes

In Type 1 diabetes, there are autoantibodies present in the blood that can be measured to confirm Type 1 diabetes. There are four types of antibodies that can cause Type 1 diabetes. They can all be measured in the blood and are usually present at diagnosis. They are:

• Glutamic acid decarboxylase (GAD) antibody

This antibody is specific against GAD. It’s common as the first detected autoantibody in childhood up to 15 years of age. Adult-onset cases most often present with this antibody. It’s associated with slower progression to Type 1 diabetes and is often found as a single-positive antibody, especially in adults.

• Insulin autoantibody (IAA)

This antibody is specific against insulin. It’s common as a first detected autoantibody in young children. Its frequency declines with age but is of little information in people already injecting insulin as antibodies can develop in response to injected insulin.

• Insulin antigen 2 auto antibody (IA-2A)

Also known as ICA512, this antibody is against tyrosine phosphatase islet antigen-2. Its presence is associated with more advanced islet auto-immunity and a faster progression to Stage 3 Type 1 diabetes.

• Zinc transporter 8 auto antibody (ZnT8A)

This antibody is against transmembrane zinc transporter type 8 protein in the beta cell granule. The presence of this antibody can improve risk stratification in individuals with a single other autoantibody.

Usually more than one antibody is present at diagnosis.

Diagnosis

Type 1 diabetes can de classified in three stages. These stages are determined by the presence of antibodies and the amount of abnormal glucose measurements.

Stage 1

The person’s blood tests positive for two or more antibodies but the person is without symptoms and the oral glucose tolerance test (OGTT) is normal.

An oral glucose tolerance test is a blood test where a person consume 75 gram of glucose and blood is tested at fasting, 30-, 60-, 90-, and 120 minutes.

The fasting plasma glucose is below 5.6 mmol\L and the two-hour OGTT is below 7.8 mmol\L. HbA1c below 5.7%. The person is asymptomatic.

Stage 2

The blood tests positive for two or more antibodies, and the oral glucose tolerance test is impaired but not yet in the diabetes range. This mean the fasting plasma glucose value is below 5.6 and 6.9 mmol/L and the two-hour OGTT is more than 11.1 mmol/L at 30-, 60-, and 90 min. The HbA1c is between 5.7 and 6.4%.

Stage 3

Antibodies are positive, the person is symptomatic, and glucose is in the diabetes range. Fasting glucose more than 7 mmol/L and two hours after meals more than 11.1 mmol\L. HbA1c more than 6.5%. The treatment for Stage 3 diabetes is insulin.

Advice for stages

Stage 1 Type 1 diabetes

1. Confirm the autoantibody three months later with a second sample.
2. Metabolic monitoring with glucose testing for the first two years after testing positive. Monitor the glucose thereafter every six months or if symptomatic.

Stage 2 Type 1 diabetes

1. Use HbA1c every six months to monitor glucose.
2. Combine with diabetes diet and exercise.
3. The question when to start early insulin to preserve beta cells of the pancreas will be decided by a specialist.

Latent auto immune diabetes of adults

Half of all the new cases of Type 1 diabetes is now occurring in adults. Misclassification due to misdiagnosis (commonly as Type 2 diabetes) occurs in nearly 40% of people.

The term latent autoimmune diabetes of adults (LADA) was introduced 30 years ago to identify adults that developed immune-mediated diabetes. The criteria for the diagnosis of LADA consists of:

• Age older than 30 years
• Lack of the need for insulin for at least six months
• Present of autoantibodies

However, there is a debate whether the term LADA should still be used. The American Diabetes Association standard of care notes that for classification purposes all forms of diabetes mediated by autoimmune destruction are included in the classification of Type 1 diabetes.

The investigation of adults with suspected Type 1 diabetes isn’t always straightforward. The first step is to suspect this in a non-obese patient with high glucose (more than 16.7 mmol/L and can present with mild acidosis). An antibody test should be done to confirm the presence of autoimmunity.

This will mark the progression to severe insulin deficiency. It’s important to remember to only check GAD antibodies in clinically suspected Type 1 diabetes since a low concentration of GAD antibodies can be seen in Type 2 diabetes and thus false positivity is a concern.

Just to make the scenario more interesting, there is 5–10% of Type 1 diabetes that may occur without antibodies and the autoantibodies disappear over time.

Genetic risk scoring (GRS) for Type 1 diabetes has received attention to differentiate people whose classification is unclear. This was developed in 2019 and uses 67 single nucleotide polymorphisms from known autoimmune loci and can predict Type 1 diabetes in children of European and African ancestry. It’s not routinely available yet for clinical use.

Investigating adults with suspected Type 1 diabetes

Step 1

Test for autoantibodies; if this is positive the diagnosis is confirmed.

Step 2

If the autoantibody test is negative, check the age (since 5–10% of Type 1 can test negative). If older than 35 years, the classification is unclear. A trial of non-insulin therapy can be started.

Do a C-peptide blood test to determine the amount of insulin from the pancreas. C-peptide with a value of more than 600 pmol/L confirms the diagnosis of Type 2 diabetes. A value between 200 and 600 makes the diagnosis indeterminate and the C peptide should be followed up in five years. Keep a good eye on glucose management.

A C-peptide value of less than 200 pmol/L moves the scale over to Type 1 diabetes.

Psychosocial care

The testing and positive screening of an autoantibody that predicts Type 1 diabetes can be very stressful to both the patient and their families. Shock, grief, guilt, anger and depression can all be emotions that may be encountered. The TEDDY study and the Autoimmunity Screening for Kids (ASK) study showed these emotions in children testing positive.

Psychosocial care should be integrated into these patients’ routine medical visits. Unfortunately, the medications tested to preserve beta cells of the pancreas in Stage 1 and 2 haven’t shown any results yet.

The quest for insulin beta cell replacement and autoantibody suppression is ongoing. As our understanding of the immunology of Type 1 diabetes expands, development of the next generation of immunotherapy is under active pursuit.

References

1. Fourlanos S, Dotta F et al. “Latent autoimmune diabetes in adults (LADA) should be less latent.” Diabetologia 2005; 48:2206-12
2. Lynam A, McDonald T et. al.” Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults age 18-50 years.” BMJ 2019;9
3. Holt RIG et.al. Investigating suspected type 1 diabetes. Diabetes care 2021;44:2589-625
4. Philip M, Achenbach P et al. “Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.” diabetology, 2024;67:1731-1759

– OTHER INTERESTING READS –

Aspen Pharmacare Holdings Limited announced last year the local availability of Eli Lilly’s tirzepatide.

Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide (GIP)receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, used as an adjunct to diet and exercise to treat adults with insufficiently controlled Type 2 diabetes, which has been approved by the South African Health ProductsRegulatory Authority (SAHPRA).

On 30 August 2023, Aspen announced that it had entered into a distribution and promotion agreement with Lilly to extend access to Lilly’s innovative portfolio of medicines to patients in South Africa and the rest of Sub-Saharan Africa.

Stephen Saad, Aspen Group Chief Executive said, “Aspen values our relationship with Lilly and its recognition of Aspen as its chosen partner inSouthern Africa to assist in contributing towards arresting non-communicable diseases (NCDs) which include cardiovascular diseases, cancer and diabetes.”

“Tirzepatide is one of the therapeutic options available to physicians for the treatment of Type 2 diabetes, which has doubled in recent times¹, with one in two diabetic patients in South Africa being undiagnosed.² A strong link is evident between diabetes, heart disease, and obesity which triggers the metabolic-cardio-renal complex³ and which poses a significant financial and public health threat to an already over-burdened healthcare system, impacting lives and livelihoods. Tirzepatide represents an added therapeutic option to address the rising tide of NCDs. It will increase access and can significantly improve related health outcomes.”

Tirzepatide has been available in SA during since December 2024 in single-dose vials, with a KwikPen® presentation currently under evaluation at SAHPRA.

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