Improving Treatment Outcomes for Patients with Diabetes Mellitus Type-2 with Glucagon-Like Peptide-1 Receptor Agonists-Experts View

Dr. Kasadha Nasser

Diabetes mellitus is a metabolic disorder associated with abnormal carbohydrate & lipid homeostasis leading to persistent elevation in plasma glucose & dyslipidaemias. If you are diabetic, your body isn’t able to properly process and use glucose from the food you eat.

The words Diabetes & Mellitus are derived from Greek word diabetes meaning siphon-to pass through, and Mellitus meaning sweet.

The term diabetes was coined by Apollonius of Memphis around 250 BC. It was in 1675 that Thomas Willis added the word “Mellitus” to the word diabetes. This was because of the sweet taste of urine, which had been noticed by the ancient Greeks, Chinese, Egyptians, Indians and Persians as evidenced in their literature  

The number of people with diabetes rose from 108million in 1980 to 422 million in 2014(WHO diabetes fact sheet 2021). In 2019, diabetes was the ninth leading cause of death with an estimated 1.5 million deaths directly caused by diabetes. 

Over the past decade, diabetes has risen faster in low and middle-income countries, Uganda inclusive than in high income countries (WHO Global report on diabetes 2016). The percentage of death caused by high blood glucose or diabetes that occur prior to age 70 is higher in low and middle-income countries than in higher income countries  

In one study conducted by silver Bahendeka and colleagues in 2016, it pointed out that diabetes in Uganda population was still low giving an opportunity for primary prevention. However, it’s estimated that most people in Uganda are unaware or just undiagnosed risking to only fatal diabetes complications 

When to see a clinician

Patients are advised to seek clinical attention when they experience these symptoms; increased thirst, frequent urination, unplanned weight loss, weak or tired feeling and frequent unexplained infections, dry mouth, slow healing wounds, blurred vision, decreased sex drive/erectile dysfunction in male, dry & itchy skin and frequent yeast infection in women. Avoid self treatment only based on these symptoms as there are other numerous medical conditions that can present with same or related symptoms 

Risk factors

The following factors may predispose you to type 2 diabetes  

Family history (parent or sibling) of diabetes, Excess weight, Physical inactivity, Age, 45 or older, History of gestational diabetes & Smoking 

Economic impact of diabetes 

Diabetes and its complications may bring about substantial economic loss to people affected and their families, to health systems and national economies through direct medical costs and loss of work & wages. Cost of patient care for people with diabetes may be high and intolerable to a major proportion of our population given the current economy stature thus living them with no tangible decision regarding diabetic care 

It should be noted that diabetes can be treated and its consequences avoided sticking to recommended diet, physical activity, regular screening, medication, complication management coupled with creating more awareness in primary health care practices 

What’s available for the clinician and patients?

Basing on current guidelines, the incretin system which includes Glucagon-like peptide-1(GLP-1) & Dipeptidyl peptidase-4 among other mediators performs multiple actions to modulate nutrient absorption and glucose homeostasis

GLP-1 is secreted after food intake and acts to slow gastric emptying promote satiety, enhance glucose dependent insulin secretion & decrease hepatic glucose production. Glucose insulinotropic polypeptide (GIP) is another incretin hormone that stimulates glucose dependent insulin secretion from beta cells, although this response isn’t robust as with Glucagon-like pepetide-1 receptor agonists (GLP-1RA), recommended by ADA guidelines 2021.

The incretin effect is believed to be blunted in patients with controlled type 2diabetes, but pharmacologically increasing GLP-1 is believed to revive insulin secretion  

Two classes of antidiabetic drugs have been developed to take advantage of the precious incretin system in treatment of Type 2 diabetes. 

According to WHO diabetes facts sheet 2021, Type 2 diabetes results from body’s ineffective use of insulin, greater than 95% of people with diabetes have type 2 diabetes, which is highly said to be as a result of physical inactivity and excess weight. 

The majority of people with diabetes are affected by type 2 diabetes. This used to occur almost entirely among adults, but now occurs in children too. 

Our discussion will focus on the robust highly efficacious GLP-1RAs. GLP-1RAs act by potentiating GLP-1 receptor signaling thus increasing GLP-1levels in the body

Why GLP-1RAs

The GLP-1RAs are preferred agents for treating type 2 diabetes (T2D) when there is a compiling need to minimize hypoglycemia or the minimize weight gain/ promote weight loss 

In head-to-head trials, GLP-1RAs, have been shown to lower A1C by ~0.8-1.6% (0.65%) more than DPP4 inhibitors, body weight by ~1-3kg, blood pressure and Lipids( Htike ZZ, Zaccardi F & colleagues)

A recent update to the American Heart Association/American Diabetic association(AHA/ADA) guidelines on Cardiovascular Disease prevention in patients with Type 2 diabetes brings forth weight management as a key component and suggests that clinicians consider prescribing antihyperglycemic drugs that produce weight loss including GLP-1RAs (Andersen, Christensen, Knop, & Vilsbøll, 2019)

Persons living with type-2 diabetes are at an increased risk of cardiovascular complications and thus cardio protective therapies or those with no evidence of cardiovascular events should be entertained to optimize patient outcome and prescriber satisfaction 

In a network meta-analysis of 60 clinical trials, GLP-1RAs have been shown to decrease systolic blood pressure-SBP(Deborah Hinnen-2017) making them ideal prescription drugs in diabetic patients with hypertension, cutting costs and decrease in pill burden  increasing adherence and tolerance in turn.

GLP-1As lipid improvement profile have been shown through significant reduction in LDL cholesterol thus ideal for our patients with dyslipidaemias which have been evident in diabetic patients 

Recommendations/advice to prescribers   

According to the American association of Clinical Endocrinology (AACE) & American Diabetes Association(ADA), diabetic treatment algorithms for glycemic control, GLP-1RAs are recommended as first line therapy as an alternative to Metformin, a biguanide in patients who can cont tolerate or are contraindicated for Metformin 

Also GLP-1As are recommended as add-on therapy for patients who do not archive their A1C target after three months of Metformin therapy. moreover Glucagon like peptide-1 receptor agonists are well suited for early use in patients with type 2 diabetes for they stimulate insulin secretion and glucagon release only when blood glucose concentration are elevated thus carrying low risk of hypoglycemia

These agents are available for twice & once daily doses and also once weekly dosing 

The following combination therapies are recommended and evidenced; 

  1. According to Garber AJ & colleagues 2016, GLP-1RAs are recommended in combination with Metformin in patients who fail to achieve A1C target with Metformin Alone
  2. GLP-1RAs can be used in combination with metformin & sodium glucose Cotransporter-2 inhibitor in patients with  persistent hyperglycemia and overweight 
  3. Moreover when used with basal insulin, GLP-1RAs may delay use of bolus mealtime insulin thus reducing incidence of hypoglycemia. Also, use with insulin provides for reduced doses and thus help mitigate weight gain often associated with intensified insulin use 

Shared decision making (SDM)

The effective management of type 2 diabetses requires Sustained self management by patients to optimize glycemic control and treatment outcomes 

Clinicians can play an important role in supporting patient’s self care efforts through good communication, patient education & problem solving 

Patients and healthcare providers are encouraged to engage in person-centered collaborative care, which involves shared decision-making (SDM) for treatment selection & ongoing monitoring.

SDM is a collaborative process in which patients & clinicians work together to identify reasonable management options for the unique situation of each patient 

SDM can help patients and clinicians to make informed choices, including selecting therapy that suits individual patient needs, values and preferences 

To my fellow prescribers 

All T2D patients should participate in diabetes self management education & should receive necessary support to acquire knowledge, master decision making and obtain skills needed for diabetes self-care 

Let’s fully assess our patients as a whole and individualize therapy always.  Diabetes mellitus is beyond looking at mere laboratory results but rather exploring patient’s environment taking into account their day today life style, food insecurities & their knowledge about different foodstuffs 

Fully explore other comorbidities and risk factors the patient may present with and prescribe just in light of best outcomes for each while avoiding pill burden thus increasing therapy tolerance with markedly reduction in adverse effects 

A personalized approach involving 6Ps (Pathology, Potency, Precautions, Perks, Practicalities, & Price) has been proposed in selecting the most appropriate therapy and optimize treatment choices in individuals with diabetes 

Establish clinician-patient shared decision making approach as the patient will feel valued and empowered in making decisions about their own health taking into account their strength and weakness. This will improve treatment adherence and honoring subsequent appointments.

Clinicians should note that dishonoring clinic appointments holds a significant percentage to causes of avoidable comorbidities and death in patients with chronic illnesses and thus should invest much in patient follow-up.

To the entire prescribing fraternity, let’s entertain ourselves in looking out for the proper medicines for our patients without getting stuck to only one type of medicine irrespective of no intended results over time for patients  

Advise to our dear patients 

As patients, you should be able to ask your clinician his/her target while initiating antidiabetic therapy not just merely taking and continuing medicines 

Good disease/disorder outcome/prognosis is beyond taking drugs alone. Kindly avoid continuing your 1, 2, 3, 5 years etc anti-diabetes prescribed drugs without clinic visits and follow up by your general practitioner/clinician.

Strictly avoid advising other patients in your circles to just buy drugs similar to yours since they were prescribed to you by a clinician, as every patient’s health is addressed as an individual  

Ensure physical activity, i.e walking for 30 minutes five days a week, making it 150 minutes. Moreover this doesn’t have to happen at once for beneficial results. Five minutes in morning, 10 minutes at lunch, and 15 minutes in the evening

Perceptions change; diabetes isn’t for the” rich” but for all that are living

Last but not least, we encourage all diabetic and prediabetic patients to get personal clinicians or make diabetic groups where a specific clinician can always give a group visit for proper follow up and support 

This article was motivated/inspired by the November 14th 2021 World Diabetic day cerebrations.
Support, spread love and hope to our diabetes patients today & optimize quality of care (QoC)

The author; Kasadha Nasser is a general practitioner, (BcmCh). 
Chairperson; BCMCH Graduate Society of Uganda, 
Tel +256 703706927 (watsapp & telegram)
@Nasser99kasadha (twitter) | Email: 

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