Personalizing Treatment For Better Disease Outcomes
20 Jul 2022
As mortality and morbidity from lifestyle diseases continue to rise, we talk about a topic close to the hearts of Filipinos: cardiovascular disease and Diabetes Mellitus Type 2, and how they significantly impact their lives physically and financially. In this webinar sponsored by ZP Therapeutics entitled Leaps and Bounds: Evolving Priorities in Managing Type 2 Diabetes, we team up with 3 amazing speakers all renowned in their fields: Dr. Cynthia De Lara, Interventional Cardiologist, Associate Professor at the UST Faculty of Medicine and Surgery and the Chief of the of Section of Cardiology at Jose Reyes Memorial Medical Center; Dr. Bien Matawaran, Endocrinologist, Associate Professor at the Department of Biochemistry, Molecular Biology and Nutrition, at the UST Faculty of Medicine and Surgery, also the Past President of the Philippine Society of Endocrinology, Diabetes and Metabolism; and Dr. Kaye Estepa-Garcia, Family and Palliative Medicine Specialist and Chair of the Department of Family and Community Medicine, UP-PGH and Manila Doctors Hospital.
To open the talk, we were presented with a case study of a male in his 50s who collapsed in the parking lot. The patient was rushed to the ER during which initial tests revealed an anterior wall myocardial infarction. Despite rigorous attempts to resuscitate the patient, he eventually expired in the ER. Looking deeper into the patient’s history, it was revealed that the patient was diagnosed with Type 2 Diabetes Mellitus (DM) in his 40s, as well as hypertension and dyslipidemia. Further, he was noted to be a 15-pack-year smoker, obese, who led a sedentary lifestyle, had a poor diet, and rarely exercised. There was no established history of cardiovascular disease (CVD). His prescribed medications included Metformin 500mg three times a day, Gliclazide 80mg once a day, Linagliptin 5mg once a day, Amlodipine 5mg once a day and Atorvastatin 20mg once a day but was poorly compliant.
Was his death preventable?
Both Dr. De Lara and Dr. Matawaran agreed that the patient’s demise could have been preventable with proper and aggressive treatment. CVD remains the major cause of mortality and morbidity for individuals with DM. Specific vascular, myopathic, and neuropathic alterations have been suggested to be responsible for excessive cardiovascular morbidity and mortality in diabetes. These alterations manifest themselves clinically as coronary heart disease, congestive heart failure, and/or sudden cardiac death as seen in the presented case. ¹ Therefore, it is important for clinicians to look at the comorbidities of patients and be aggressive in terms of treatment to prevent unwanted outcomes. Compliance should also be addressed since this plays a major role in the progression of the disease. ²
Primary Prevention and Secondary Prevention
Since CVD is a major cause of mortality and morbidity, life expectancy is reduced by more than 12 years in individuals aged 60 years old with DM and previously established CVD. According to the total data of causes of death in patients with DM, the majority are due to heart attack and stroke. Because of this alarming data, Dr. De Lara reiterates that primary prevention is the ultimate goal, all the risk factors for the disease should be identified early on and the end result is to avoid death or disability. However, in the real-world setting, most patients only seek consult once they already have symptoms of the disease, therefore secondary prevention comes into play. Finally, once lifestyle diseases are diagnosed, physicians should be aggressive in addressing it. ²
Recent updates on DM management
The American Diabetes Association (ADA) released its most recent updates (2022) on the management of DM and it focused on individualization of diabetes management in terms of screening, intervention and care, use of technology, and prevention of complications. Patient-centered goals were emphasized in preventing type 2 DM. There was an evident shift from a gluco-centric to a holistic approach as the emphasis was given to a more tailored approach to management. While first line therapy generally includes metformin and comprehensive lifestyle modification, individualization was now more important. In patients with CVD and chronic kidney disease (CKD), SGLT2 inhibitors and GLP1 agonists are now recommended earlier. The importance of preventing complications was also highlighted. ³
In addressing DM in patients with comorbidities such as hypertension and dyslipidemia, clinicians should not wait for the blood sugar levels to decrease since the stepwise approach that has been used for years has been proven to delay reaching targets. When there are episodes of elevated blood sugar, micro and macrovascular complications may occur, therefore a more proactive approach should be taken, or combination therapy may be started to achieve a reduction in hemoglobin A1c levels. Treatment is now based on the goal of providing better outcomes for patients based on their needs. Dr. Matawaran highlighted that the recent star in most clinical trials is the GLP-1 agonists as it has been very effective in reducing cardiovascular events. ²
Barriers to treatment
In the local setting, one of the things that have been a hindrance to patient compliance is the costs of medications and treatments. Patients tend to shy away from newer treatments because of the intimidation of out-of-pocket costs, and they fail to look at the bigger picture and see how much savings they are getting in the long term. Another concern is the hesitancy on the initiation of injectable therapy.
Filipinos appear to be more conservative and prefer non-invasive types of treatments, often opting to delay switching or initiation of injectable therapy. Multiple studies have however proven that better and earlier compliance to the appropriate medications would actually reduce the costs as compared to the costs involved in treating further complications. ²
What Anti-DM medications work in preventing CVD?
According to the most recent recommendations, SGLT2 inhibitors and GLP-1 agonists should be started earlier in patients with CVD and/or CKD. In addition, the updated guideline reflects the adjustment to patient-centered treatment goals rather than sequential treatment to intensify treatment. ³
The addition of a GLP-1 analog should be considered in patients with a contraindication or intolerance to metformin, in patients with a hemoglobin A1c greater than 1.5% over target, or in patients who do not reach their target A1c in three months, particularly in patients with atherosclerosis, heart failure, or CKD. Aside from the reduction in cardiovascular events, GLP-1 agonists have also been demonstrated to promote weight loss. The ease of GLP-1 agonists also makes it an attractive option for patients as the dosing is less frequent and they come in a single or multi-dose injectable pen. Adverse effects are also minimal. ⁴
As seen in the most recent data, one GLP-1 agonist stands out: Dulaglutide demonstrated benefits in reducing both secondary, and more importantly, primary CV event occurrence. In the REWIND trial, which consisted of type 2 DM patients aged 50 years and older with established cardiovascular disease or multiple CV risk factors and a wide range of glycemic control, it reduced major adverse cardiovascular events as compared to placebo ⁵
Conclusion
Dr. De Lara believes that the way that we are treating patients today is much better than the treatments we had 10 years ago. Indeed, medicine has come a long way in terms of management – it is now more holistic and better addresses the individual needs of the patients. Dr. Matawaran concluded that despite the advancement in terms of treatment, compliance is still a major factor for better disease outcomes and that physicians should also take that into consideration in recommending and encouraging treatment for patients. The roles of clinicians should not stop at identifying diseases and recommending the right treatment, there is also a need to make sure that we take down the barriers the patients may face in achieving better mortality and morbidity outcomes.
To open the talk, we were presented with a case study of a male in his 50s who collapsed in the parking lot. The patient was rushed to the ER during which initial tests revealed an anterior wall myocardial infarction. Despite rigorous attempts to resuscitate the patient, he eventually expired in the ER. Looking deeper into the patient’s history, it was revealed that the patient was diagnosed with Type 2 Diabetes Mellitus (DM) in his 40s, as well as hypertension and dyslipidemia. Further, he was noted to be a 15-pack-year smoker, obese, who led a sedentary lifestyle, had a poor diet, and rarely exercised. There was no established history of cardiovascular disease (CVD). His prescribed medications included Metformin 500mg three times a day, Gliclazide 80mg once a day, Linagliptin 5mg once a day, Amlodipine 5mg once a day and Atorvastatin 20mg once a day but was poorly compliant.
Was his death preventable?
Both Dr. De Lara and Dr. Matawaran agreed that the patient’s demise could have been preventable with proper and aggressive treatment. CVD remains the major cause of mortality and morbidity for individuals with DM. Specific vascular, myopathic, and neuropathic alterations have been suggested to be responsible for excessive cardiovascular morbidity and mortality in diabetes. These alterations manifest themselves clinically as coronary heart disease, congestive heart failure, and/or sudden cardiac death as seen in the presented case. ¹ Therefore, it is important for clinicians to look at the comorbidities of patients and be aggressive in terms of treatment to prevent unwanted outcomes. Compliance should also be addressed since this plays a major role in the progression of the disease. ²
Primary Prevention and Secondary Prevention
Since CVD is a major cause of mortality and morbidity, life expectancy is reduced by more than 12 years in individuals aged 60 years old with DM and previously established CVD. According to the total data of causes of death in patients with DM, the majority are due to heart attack and stroke. Because of this alarming data, Dr. De Lara reiterates that primary prevention is the ultimate goal, all the risk factors for the disease should be identified early on and the end result is to avoid death or disability. However, in the real-world setting, most patients only seek consult once they already have symptoms of the disease, therefore secondary prevention comes into play. Finally, once lifestyle diseases are diagnosed, physicians should be aggressive in addressing it. ²
Recent updates on DM management
The American Diabetes Association (ADA) released its most recent updates (2022) on the management of DM and it focused on individualization of diabetes management in terms of screening, intervention and care, use of technology, and prevention of complications. Patient-centered goals were emphasized in preventing type 2 DM. There was an evident shift from a gluco-centric to a holistic approach as the emphasis was given to a more tailored approach to management. While first line therapy generally includes metformin and comprehensive lifestyle modification, individualization was now more important. In patients with CVD and chronic kidney disease (CKD), SGLT2 inhibitors and GLP1 agonists are now recommended earlier. The importance of preventing complications was also highlighted. ³
In addressing DM in patients with comorbidities such as hypertension and dyslipidemia, clinicians should not wait for the blood sugar levels to decrease since the stepwise approach that has been used for years has been proven to delay reaching targets. When there are episodes of elevated blood sugar, micro and macrovascular complications may occur, therefore a more proactive approach should be taken, or combination therapy may be started to achieve a reduction in hemoglobin A1c levels. Treatment is now based on the goal of providing better outcomes for patients based on their needs. Dr. Matawaran highlighted that the recent star in most clinical trials is the GLP-1 agonists as it has been very effective in reducing cardiovascular events. ²
Barriers to treatment
In the local setting, one of the things that have been a hindrance to patient compliance is the costs of medications and treatments. Patients tend to shy away from newer treatments because of the intimidation of out-of-pocket costs, and they fail to look at the bigger picture and see how much savings they are getting in the long term. Another concern is the hesitancy on the initiation of injectable therapy.
Filipinos appear to be more conservative and prefer non-invasive types of treatments, often opting to delay switching or initiation of injectable therapy. Multiple studies have however proven that better and earlier compliance to the appropriate medications would actually reduce the costs as compared to the costs involved in treating further complications. ²
What Anti-DM medications work in preventing CVD?
According to the most recent recommendations, SGLT2 inhibitors and GLP-1 agonists should be started earlier in patients with CVD and/or CKD. In addition, the updated guideline reflects the adjustment to patient-centered treatment goals rather than sequential treatment to intensify treatment. ³
The addition of a GLP-1 analog should be considered in patients with a contraindication or intolerance to metformin, in patients with a hemoglobin A1c greater than 1.5% over target, or in patients who do not reach their target A1c in three months, particularly in patients with atherosclerosis, heart failure, or CKD. Aside from the reduction in cardiovascular events, GLP-1 agonists have also been demonstrated to promote weight loss. The ease of GLP-1 agonists also makes it an attractive option for patients as the dosing is less frequent and they come in a single or multi-dose injectable pen. Adverse effects are also minimal. ⁴
As seen in the most recent data, one GLP-1 agonist stands out: Dulaglutide demonstrated benefits in reducing both secondary, and more importantly, primary CV event occurrence. In the REWIND trial, which consisted of type 2 DM patients aged 50 years and older with established cardiovascular disease or multiple CV risk factors and a wide range of glycemic control, it reduced major adverse cardiovascular events as compared to placebo ⁵
Conclusion
Dr. De Lara believes that the way that we are treating patients today is much better than the treatments we had 10 years ago. Indeed, medicine has come a long way in terms of management – it is now more holistic and better addresses the individual needs of the patients. Dr. Matawaran concluded that despite the advancement in terms of treatment, compliance is still a major factor for better disease outcomes and that physicians should also take that into consideration in recommending and encouraging treatment for patients. The roles of clinicians should not stop at identifying diseases and recommending the right treatment, there is also a need to make sure that we take down the barriers the patients may face in achieving better mortality and morbidity outcomes.