Metformin and GLP-1s and Insulin—Oh My! Establishing Individual Priorities in Type 2 Diabetes Treatment

By Ashlyn Smith, MMS, PA-C, DFAAPA, LSC

ELM Endocrinology & Lifestyle Medicine

Managing Type 2 Diabetes can feel overwhelming when trying to balance pills, injections, which ones need to be taken with food, which are daily or weekly or multiple times a day, and knowing the side effects to look for. Thankfully, this paradox of choice has an important benefit: CHOICE!

Managing diabetes is no longer a step-by-step mission: add this medication first, then this one, then this one. Treatment is now individualized to YOUR specific needs! Whether the focus is on weight management, prevention or improving complications, avoiding hypoglycemia, or navigating pill or injection burden, options can be tailored to meet your goals.

Type 2 Diabetes treatment options now come with perks and considerations beyond sugar--That means your meds can now do more for you.

If medication isn’t just about lowering blood sugar, what else should we be considering?

Heart and kidney disease

Many glucose-lowering medications have fringe benefits that can be used to improve health or reduce the risk of complications. The first step in selecting a medication is knowing whether or not you have and kidney, circulation, or heart issues related to diabetes. If you do, the first priority is picking a diabetes medication that does double-duty to lower glucose AND help reduce the risk of further complications. That is like getting two (or more) benefits for the price of one:

These can help:

·       SGLT2 inhibitors: These once daily pills lower glucose without a high risk of hypoglycemia and do not need to be taken with meals. Many variations in this category help reduce the risk of heart disease, heart failure, stroke, or kidney disease. One might also see modest weight loss and blood pressure reduction, too.

·       GLP-1 or GLP/GIP agonists: The injectable medications gained popularity in the recent years due to their weight loss benefit which we will address a bit later. Whether you take the medication daily or weekly, many medications in this class help reduce the risk of heart attack, stroke, and even kidney disease. There is some evidence that these medications help slow down the progression of diabetes.

These can hurt:

·       Sulfonylureas: This class includes the “g’s”: glipizide, glimepiride, and glyburide. A major side effect of these medications is low blood sugar, which is stressful on an already-compromised heart. Additionally, the risk of low blood sugar is worse in kidney disease.

·       DPP4 inhibitors: Medications in this class are daily pills and include the “gliptins.” While not harmful to the kidneys, the dose will need to be adjusted depending on the stage of kidney disease.  This class should be avoided if you have a history of certain stages of heart failure.

·       Pioglitazone: There is only one remaining medication in this class. Pioglitazone is a pill taken once a day and does not require food to take. This medication should be avoided if you have a history of heart failure. There is no known risk to taking this medication in kidney disease.

·       Metformin: There is only one medication in this class so the class is referenced as the medication itself. Metformin is a pill that can be taken once a day or twice a day depending on the dose. As we saw with DPP4 inhibitors, metformin does not cause kidney damage itself, but clearing the medication can add stress to kidneys that are already compromised. In certain stages of kidney disease, the dose will need to be adjusted or avoided altogether.

Avoiding hypoglycemia (low blood sugar)

Low blood sugar is a concern for all clinicians and certainly anyone living with diabetes. In addition to feeling terrible, hypoglycemia can be dangerous. Low blood sugar is associated with increased risk of falls, seizures, heart arrhythmias, and death. Additionally, even mild hypoglycemia can be dangerous in certain situations such as driving, operating heavy machinery, a history of seizures, a history of atrial fibrillation, or anyone 65 years old or older. Individuals with kidney disease are particularly susceptible to having low blood sugar since the kidneys cannot clear out medications as well. If you have experienced a severe hypoglycemia episode where you needed outside assistance to treat it, there is a higher risk of having severe hypoglycemia again. In all of these cases, the priority is placed on choosing diabetes medications with a low risk of hypoglycemia.

These can help: All the following medications have LOW risk of hypoglycemia

·       SGLT2 inhibitors 

·       GLP-1 or GLP/GIP agonists

·       DPP4 inhibitors

·       Metformin

·       Pioglitazone

These can hurt: These medications carry a risk of low blood sugar, either when taken by themselves or in combination with any other diabetes medications

·       Sulfonylureas

·       Insulin

Managing weight

While not everyone with Type 2 Diabetes has overweight or obesity, these medical conditions tend to come together. We know that a higher body weight tends to worsen insulin resistance and lead to higher medication doses as well as more medications in general. Similarly, higher weight is associated with a risk of high blood pressure, high cholesterol, sleep apnea, fatty liver, and more. Losing weight is particularly challenging in the setting of metabolic issues such as diabetes. In those with overweight or obesity, the priority is selecting medications that are weight-neutral (keep weight about the same) or are associated with weight loss.

These can help:

·       SGLT2 inhibitors: These medications are associated with modest weight loss. This class works by pushing glucose out via the urine, and glucose is calories. Therefore, if you are losing glucose, you are losing calories.

·       GLP-1 or GLP/GIP agonists: These classes are associated with more significant weight loss due to lowering hunger signals (the brain thinks you are less hungry) and delaying gastric emptying (the gut mechanically feels fuller). However, if the gut is slowed down too much, nausea or other gastrointestinal issues can occur.

These are neutral:

·       DPP4 inhibitors: There is no link between this class of medications and weight gain or weight loss.

·       Metformin: There is a theoretical weight loss associated with this medication, though it does not have an official indication for weight loss. Metformin works to lower insulin resistance, which lets your body make less insulin or can allow you to inject less insulin. As you will see below, that can have an impact on weight.

These can hurt:

·       Sulfonylureas: This class stimulates your body to make more insulin in order to bring down glucose. However, insulin is a fat-storing hormone so weight gain can be an unintended side effect.

·       Pioglitazone: While this medication can reduce fatty liver, it is associated with weight gain due to increased overall fatty tissue as well as potential fluid retention.

·       Insulin: Similarly, injecting insulin is associated with increased weight since insulin itself is a fat-storing hormone. Importantly, the weight gain seen with insulin is directly proportional to the amount of calories the body is able to absorb. There are some scenarios where insulin is required for safety, such as very high glucose levels, advanced disease, symptoms of diabetes, or a low insulin reserve. In these cases where insulin must be used, the weight gain can be mitigated by adding other diabetes medications that are weight-neutral or help reduce weight.

Injection or pill burden

Because of the complexity of diabetes, it often requires multiple medications to achieve blood sugar control. Additionally, most people living with diabetes have many other conditions that require medication such as high blood pressure and cholesterol. Every person managing diabetes is different: some can manage multiple medications easily; some find it challenging to remember to take medications multiple times a day; some do not have the dexterity or support to inject medications; some are tired of taking so many pills and would prefer injections; some are concerned about injections and would prefer pills.

These can help:

·       Weekly GLP-1 or GLP/GIP agonists: Decreasing medication to once a week may be more convenient than taking medications daily or multiple times per day.

These might help: These medications are taken once a day so they may be less burdensome than other classes.

·       SGLT2 inhibitors

·       DPP4 inhibitors 

·       Pioglitazone

·       Basal (or background) insulin, though this class might be taken twice a day

These can hurt: These classes might be taken once a day but are usually taken multiple times a day and often have to be taken with food.

·       Sulfonylureas 

·       Metformin

·       Bolus (or mealtime) insulin

Cost considerations

For those on a budget or having to manage multiple copays, it can be challenging to take medications consistently. Some people living with diabetes might feel the need to skip filling their prescriptions from time to time or perhaps space out their medication to help it last longer. This leads to higher glucose levels, A1c, and complication risk. In these cases, it is unrealistic to simply say “take your medications.” Cost-saving options can be employed to help lower the burden of paying for diabetes medications. For commercial insurance, many branded medications have copay assistance cards. Others may be associated with financial assistance programs. Prescription copays can vary significantly depending on which pharmacy is used. Mail order pharmacies sometimes offer discounts on copays due to “buying in bulk.” These cost-saving steps are important to explore if you have evidence of kidney, heart, or circulation issues and would benefit from the medications that help reduce your heart and kidney risks. However, if cost continues to be a major factor after these cost-saving steps  priority is utilizing generic medications which are often lower cost. Carefully consider the risks versus benefits of choosing lower-cost medications.

These can help: The medications in this section are generic.

·       Sulfonylureas

·       Metformin

·       Pioglitazone

·       Some insulins

These might help: If copay cards or other cost-saving options are available, these may be an option.

·       SGLT2 inhibitors

·       DPP4 inhibitors 

·       Weekly GLP-1 or GLP/GIP agonists

·       Some insulins

How I can help support you with establishing priorities in Type 2 Diabetes

·       I engage you in establishing your individualized priorities at every visit

Throughout your diabetes journey, we will discuss many topics including medication options to optimize or initiate or stop based on your specific needs and the specific concerns we are addressing at that time. During every visit, we will discuss priorities that I am seeing (such as evidence of heart or kidney disease) and concerns that you are seeing (such as side effects, cost, pill/injection burden, something else, or a combination of concerns). I directly include you in the “why” of certain medications, not just prescribe something and see you in three months. Understanding the rationale for or against certain medication options helps empower you to ask questions and be an active participant in treatment choices.

·       I create an environment without shame

At ELM, we talk about hard topics without shame or blame. You are human so it is normal to struggle sometimes and not others, to forget medications, to skip medications because of side effects/cost/misunderstanding, and more. Open-ended questions about challenging issues helps normalize these human factors and helps foster a more honest, collaborative patient-clinician relationship. When we can address barriers openly, we are better able to find or adjust the plan to work best for you where you are at that time.

·       We work together on your optimal diabetes plan

I seek out your input and engagement so we collaborate together to both lower glucose and A1c as well as address the non-glycemic goals that are most essential to you and your case. By facilitating active engagement, you become a more empowered and healthier patient. The collaboration does not end when a medication is started or a dose adjusted. The patient-clinician conversation continues to assess how the medication changes have or have not improved management. The conversation continues over the long-term—I actively seek out and want to hear from you! What worked? What didn’t? What may have changed since we last spoke? No need to wait until your next scheduled appointment to bring up any concerns or questions. I am here for you whenever you need—diabetes doesn’t take a break, so neither does our work together.

Take home message:

Diabetes treatment is more than just lowering glucose and A1c. An individualized treatment approach focuses on the priorities that you have and that your body needs. Whether we need to focus on reducing hypoglycemia risk, lowering injection or pill burden, weight management, or heart and kidney protection, medications can do more. Collaborative diabetes management means that we discuss what the priorities are for you where you are in your diabetes journey and the “why” behind medication options, leading to a personalized approach to diabetes management.

Have more questions about diabetes treatment options? I am here to help—let’s connect on a free educational consultation to discuss further!

Access additional information in the free resource designed to empower patients on diabetes management from the American Diabetes Association!

Disclaimer:

The content on this blog is for informational purposes only and is not intended to provide medical diagnosis, treatment, or replace professional medical advice, diagnosis, or care. Always consult a qualified healthcare provider with any questions regarding a medical condition or treatment.