EVERGREEN Webinar: Clinical FAQs on T2DM Care, Addressed by Dr V Mohan

Dr. V. Mohan, M.D., FRCP (London, Edinburgh, Glasgow & Ireland), Ph.D., D.Sc. D.Sc (Hon. Causa), FNASc, FASc, FNA, FACE, FACP, FTWAS, MACP, FRSE. Dr. V. Mohan is a Padma Shri Awardee and is the Chairman, Dr. Mohan’s Diabetes Specialities Centre in Chennai, South India, an IDF Centre of Excellence in Diabetes Care and Madras Diabetes Research Foundation, Asia’s largest stand-alone diabetes research center.

Below are the highlights from the discussion:

Moderator: The DPP4 inhibitors, widely used and proven effective in Indian studies over two decades since their launch, have garnered extensive clinical experience across numerous patients with type 2 diabetes mellitus (T2DM). They are now emerging in combination with SGLT2 inhibitors. Where do you envision this combination being positioned in clinical practice?

Dr V Mohan: The combination of DPP4i and SGLT2i can be utilized at any stage of diabetes and regardless of whether the patient is obese and with or without cardiovascular or renal risk. In patients with high A1C levels, using Dapagliflozin or Linagliptin alone may not achieve the target, as evidenced by the ICMR-INDIAB study which demonstrated the ongoing challenge of reaching metabolic target goals, even at a national level. Therefore, using a combination of two of the best oral antidiabetic drugs will effectively manage glycemia and protect the heart and kidneys while also offering additional benefits such as weight reduction, blood pressure control, and decreased risk of genital tract infections (GTI), thus potentially benefiting patients with type 2 diabetes mellitus (T2DM).

The profile of T2DM varies, with certain patients being diagnosed early, while others may present with comorbidities such as obesity, hypertension, dyslipidemia, and heart failure. These drugs can be safely prescribed to patients across all these profiles.

Regarding renal safety, Linagliptin is deemed safe across the spectrum of chronic kidney disease (CKD), even in cases of severe renal failure. Dapagliflozin is considered safe for patients with estimated glomerular filtration rates (eGFR) ranging from 20 to 30 ml/min/1.73m²; below this threshold, it is recommended to avoid use of SGLT2 inhibitors.

There are a few cases where DPP4i and SGLT2i should be avoided. Linagliptin should be avoided in cases of acute and chronic pancreatitis; SGLT2 inhibitors are not recommended for patients who are weak, frail, have low blood pressure, experience dizziness, have an imbalance of electrolytes, are sick, or are hospitalized.

Otherwise, in every T2DM patient with or without comorbidities, the combination of linagliptin and dapagliflozin can be used.

Moderator: In your presentation, you showcased a case of managing a T2DM patient with deranged liver parameters; how important is it to conduct liver function tests or renal function tests in patients with T2DM, and how frequently should one perform them?

Dr V Mohan: It is routine to conduct LFT and RFT on every patient with type 2 diabetes (T2D). Without knowledge of renal function, prescribing medication is not feasible; everything relies on eGFR. Therefore, urea, creatinine, albumin, and eGFR are essential for every patient. I tend to repeat GFR on every visit. LFT should ideally be done once a year or every six months. If fibroscan is available, it could be included in the routine.

I believe that the approach to managing diabetes has evolved from a glucose-centric approach to a cardio-renal-metabolic approach, necessitating a holistic perspective.

Moderator: How early and common is fatty liver in type 2 diabetes patients?

Dr V Mohan: A bidirectional relationship exists between fatty liver and type 2 diabetes (T2D). Fatty liver can lead to the development of T2D, and vice versa. Both conditions can also coexist. Once fatty liver develops, there is insulin resistance, potentially leading to beta cell exhaustion and the onset of diabetes. Similarly, uncontrolled diabetes and dyslipidemia, as seen in one of the cases, can lead to the conversion of free fatty acids into triglycerides, which are then deposited in adipose tissue, contributing to fatty liver. Therefore, diabetes can also contribute to the development of fatty liver. However, there are drugs available that can aid in weight loss, correct fatty liver, and control glycemia.

Moderator: Sir, in your presentation, you mentioned that "In the life of a diabetic patient, the requirement of insulin is a must," and you have always advocated for insulin as an initiation therapy. How do you view the combination of linagliptin and dapagliflozin along with insulin?

Dr V Mohan: Early and aggressive insulin therapy has changed the natural history of diabetes, improving beta-cell function, eliminating lipotoxicity and glucotoxicity, and lowering C-peptide levels.

However, the issue with aggressive insulin therapy is weight gain. Some patients are given high insulin doses (40-50 units), resulting in significant weight gain. In such cases, the use of a DPP-4 inhibitor, SGLT2 inhibitor, or a combination of both agents can substantially reduce the need for insulin doses and prevent weight gain. Quite often, there are high instances of patients discontinuing insulin doses altogether.

There are certain drug combinations, such as pioglitazone and insulin, which increase weight and the risk of heart failure (HF). Similarly, the combination of sulfonylureas and insulin is not ideal due to the propensity for weight gain. However, Metformin, DPP-4 inhibitors, and SGLT-2 inhibitors are all safe options that help reduce insulin doses and prevent weight gain.

Moderator: Sir, you mentioned the importance of adherence in the management of T2DM. What is your take on combination therapy, where you only require a single daily dose, versus taking multiple pills?

Dr V Mohan: For the management of type 2 diabetes mellitus (T2DM), from a compliance perspective, the combination of Linagliptin and Dapaglilflozin is a clear winner. Dapagliflozin and Linagliptin, available in doses of 10 mg and 5 mg respectively, are taken once daily. However, counseling patients on medication adherence is crucial. Explaining the benefits of regularly taking medications to keep their ABC (A1C, blood pressure, and cholesterol) under control is vital.

Moderator: Sir, once again, thank you for the lucid presentation; it was very insightful. What are your final key messages for managing type 2 diabetes mellitus (T2DM)?

Dr V Mohan: I strongly believe that all of us, as doctors, diabetologists, and physicians, should aim to create a diabetes-complication-free India.

However, with the increase in obesity and family history of diabetes, producing a diabetes-free India will be very difficult. Nevertheless, if we achieve the A (A1C), B (blood pressure), C (cholesterol) goals, we should be able to prevent complications of diabetes such as retinopathy, nephropathy, neuropathy, liver disease, and CVDs. Currently, only 7.7% of individuals with diabetes in India have achieved combined ABC targets, so there is still a long way to go.

A personalized approach should be incorporated for every patient with type 2 diabetes (T2D). It is crucial to prevent clinical inertia and prescribe medications in combination without the fear of side effects including the utilization of insulin in the beginning to improve HbA1C levels if needed.

It is critical to realize that we are losing time. In the heart, we say "Time is Muscle"; similarly, in diabetes, "Time is beta cell function." If we don't control diabetes, the beta cells will get exhausted earlier, leading to permanent insulin therapy, which will further increase weight, leading to a spiral cascade. So tight glucose control is a must.

Currently, we have 136 million people with prediabetes. Early intervention in such cases with a focus on lifestyle modification, weight reduction, and steps to prevent progression to diabetes should be incorporated.

Identify those with early T2D amenable for remission and try to achieve remission wherever possible—use newer drugs wherever needed. The newer drugs have become more affordable and come with multiple benefits with very few side effects, and have stood the test of time. In India, we are very lucky to get these medicines at affordable prices. In such cases, the combination of Linagliptin and Dapagliflozin is an evergreen duo beneficial across the spectrum of T2DM. Utilizing them and ensuring that every patient achieves glucose and metabolic goals is vital. It is our duty to continuously educate our patients to achieve better results than what we have now.

Adapted from

Reference:

1. Dr V Mohan, EVERGREEN Webinar Presentation.