My patients with diabetes at their initial presentation, commonly complain about excessive weight gain and not being able to lose weight. If you feel you are one of those patients, this article is definitely for you. In this article, we are going to answer several questions. The main questions are: What causes weight gain with diabetes? What causes weight loss in diabetes? We will also talk about what diabetic medications that cause weight gain and what diabetic medications that cause weight loss?
Table of Contents
Common reasons that cause weight gain with diabetes:
#1 Insulin resistance
#2 Insulin treatment such as Lantus, Levemir, NovoLog, Humalog, Apidra, Toujeo, Tresiba, Basaglar, Novolin, Humulin
#3 Sulfonylurea treatment such as glipizide, glyburide, glimepiride
The most common reason for gaining weight with diabetes is insulin resistance. You can read more about insulin resistance in our previous blog post. To summarize, when you have insulin resistance your body creates a lot of insulin. Since insulin itself is a hormone that causes weight gain, insulin resistance creates a vicious cycle that makes it harder to lose weight.
Patients who are on insulin therapy are at high risk for weight gain. If you are on Lantus, Levemir, Humalog, NovoLog, Apidra, Fiasp, Novolin or Humulin then you are on insulin. The job of insulin is to transfer the glucose from the blood into the tissues. The tissues that need blood sugar the most are fat and muscle. Typically fat cells are faster than muscle cells to pick up glucose. So far, sounds good, right? So why do we gain weight on insulin?
Normal people’s body makes insulin when they eat, yet insulin taken from outside sources causes much more weight gain.
Why is that?
Our body makes only enough insulin to get the job done and insulin levels go down right after the sugars start coming down. However, when you are on insulin, the insulin levels in your body do not automatically go down since you have already injected a certain amount of insulin into your body. Insulin has a certain half-life and duration to be eliminated from the system. As a result, unless you perfectly match the insulin with the food you eat, your blood glucose will continue to go down and your body will be in a “hunger” state. If you give just the right amount of insulin for the food that may not be a problem, however, most people inaccurately estimate the insulin that they need or do not take insulin consistently to achieve optimal insulin to food ratio. As a result, most people end up overeating to avoid low blood sugar which leads to weight gain. On the other hand, insulin is a hormone that causes water retention. As a result, weight gain can be in the form of water retention more than fat in the beginning. Talk to your endocrinologist or diabetes specialist for alternative medications to the insulin.
Sulfonylurea such as Glipizide, Glyburide, and Glimepiride:
The way these medications work, make you prone to low blood sugars and weight gain. These agents basically whip your pancreas to make more insulin at a steady rate. On the other hand, you only need extra insulin after you eat. In between meals you do not need as much insulin. The problem is, when you are on a sulfonylurea, your body constantly makes insulin. The constantly elevated insulin levels continue to reduce your blood sugars. As a result, you start feeling more hungry than usual. Moreover, if you miss a meal you may have low blood sugar which makes you eat even more.
So, what is the solution? Avoid sulfonylureas if you can. There are definitely alternative medications to sulfonylureas. Most of the time primary care physicians will prescribe sulfonylureas because they are generic, easy to obtain and reduce blood sugars quickly. On the other hand, patients will pay the price with weight gain and frequent low blood sugars. A diabetes specialist that can appeal insurance denials, will be your best friend to get the best medications needed for your unique situation. If obtaining the quality medications that can help with weight loss and prevent low blood sugars is not easy or possible, remote glucose monitoring by your endocrinologist or diabetes specialist will also help troubleshooting problems.
Diabetes medications that cause weight loss
Metformin, GLP-1 agonist agents and SGLT2 inhibitors are commonly used in patients with diabetes to help with weight loss.
SGLT2 inhibitors are Jardiance, Invokana, Farxiga, Steglatro. We will go over these agents briefly below.
How effective is Metformin as a diabetic medication that can cause weight loss?
The only generic medication that can cause weight loss is Metformin. Weight loss with Metformin is very slight and maybe 1 to 2%. Although that is not much, it is better than gaining weight with sulfonylureas or insulin. The exact mechanism of weight loss with Metformin is not known. It is for sure that some people develop diarrhea and a metallic taste in their mouth, which may be contributing to weight loss as well. Side effects of Metformin can be tolerated if it started very slowly and the dosage is titrated gradually. Taking Metformin with meals can also help. Typically, side effects go away within 3 to 4 weeks for most patients. Yet, up to 20% of patients can still not tolerate Metformin at all.
What about Ozempic, Trulicity, Rybelsus or Bydureon? Do these diabetic medications cause weight loss?
Definitely. This class of medication is called GLP-1 agonist. These are basically gastrointestinal hormones that allow communication between the stomach and the pancreas. People without diabetes are able to secrete these intestinal hormones after they eat and initiate the pancreas to make insulin. This process is broken with diabetes. As a result, patients do not feel full on time but also do not make enough insulin to prevent high blood sugars. When you start taking these agents you start feeling fuller faster and your body will make only enough insulin to prevent excess insulin usage.
As we discussed above, when you are on insulin or sulfonylurea you are getting much more insulin than is necessary which leads to weight gain.
Ozempic, Trulicity, Bydureon and Rybelsus also directly affect the hypothalamus at the “appetite center”. So cravings become less and half the portion size can make you feel full. When your doctor or diabetes coach talks to you about weight loss, talk to them about these agents to see if it may be a good fit for you. Your diet definitely will be a lot easier on these medications. Insurance coverage for these medications can be a problem due to the higher price tags on these drugs.
In studies, Ozempic appears to be the most effective in weight loss. Trulicity and Rybelsus in my diabetes practice appear to be similarly effective. Trulicity is easier to use and I use Trulicity more often in patients with dexterity problems or patients who have never used injections and are hesitant to start using injections.
Rybelsus is the only oral GLP-1 agent as of 2020. For people who object to the idea of an injection, Rybelsus comes in handy. It is a medication that you will have to take on an empty stomach with 4 ounces of water. Patients will have to wait 30 minutes after taking the medication to eat. This can be somewhat inconvenient for many people. On the other hand, Ozempic, Trulicity, and Bydureon are once a week injections. So, it boils down to the individual patient preference.
Are there any harmful effects associated with Ozempic, Trulicity, Rybelsus, Bydureon?
Although, human studies do not indicate any increased risk of cancer there have been some reports of rats developing pancreatic or medullary thyroid cancer. So if you have a family history of these cancers you may want to rethink these agents.
Although these agents can help with weight loss, some patients (up to 10%) may not tolerate them due to side effects such as nausea, vomiting, diarrhea, and constipation. Thankfully, most side effects subside in time if the patient can persist with taking the medication.
Does Jardiance, Invokana, Farxiga or Steglatro cause weight loss?
Diabetic medications that cause weight loss include SGLT-2 class which includes Jardiance, Invokana, Farxiga, and Steglatro.
For sure, these medications work by allowing excretion of sugar from the body. Normally, kidneys do not allow excretion of blood sugars until blood sugars exceed 220 mg/dL. As a result, patients with very uncontrolled diabetes lose weight without any medication. This is not a healthy way of losing weight so definitely we did not recommend this. Some young, type I diabetic patients discover this and stop using their insulin in order to lose weight. That is close to committing suicide for most patients as they end up with DKA (diabetic ketoacidosis) which can lead to death.
Nevertheless, losing weight while controlling diabetes is not a bad idea. By using these agents, patients will be able to excrete excessive glucose between 100-200 mg/dL. This is where most diabetic patients maintain blood sugars. Without these agents, losing glucose in the urine is not possible. Up to 300-calorie per day loss is possible by using Invokana, Jardiance, and Steglatro as well as Farxiga. Due to the excretion of sugar in the urine, the risk of infection can increase with these agents. So we have to watch out for this possible side effect. Know the signs and symptoms of a urinary tract infection and pay attention to your body.
Does Invokana cause leg amputations?
Invokana recently had a negative reputation due to an increased risk of amputations. This is a blanket statement. Invokana only increases leg amputations in patients with underlying cardiovascular disorders such as clogged leg arteries, severe neuropathy, current or history of diabetic foot ulcers.
When you are on an SGLT2 inhibitor such as Invokana, Jardiance, Farxiga or Steglatro your diabetes specialist should keep an eye on diabetic foot ulcers. If you notice a diabetic foot ulcer, no matter the size, you should report to your diabetes specialist. In my practice, I typically stop these agents. It is believed that due to slight dehydration that happens with these agents, they can reduce the blood flow through the healing tissue. This can delay the healing of ulcers and can potentially progress to gangrene.
What is the DKA risk in patients taking Jardiance, Invokana, Steglatro, Farxiga?
There is a slight chance of DKA in patients taking these agents. DKA is a condition where the body starts producing a lot of ketone bodies. Strangely patients who have DKA on these agents do not have high blood sugars. For DKA to happen your body must be depleted of the insulin. So if you have any nausea, abdominal pain or vomiting on these agents you should inform your doctor immediately.
What’s the verdict?
The bottom line, there are diabetic medications that can cause weight loss. Lifestyle changes with the help of a diabetes coach and certain medications such as Ozempic, Rybelsus, Trulicity, Bydureon, Jardiance, Farxiga, Invokana and Steglatro can be used on selected patients in order to help with diabetes control as well as weight loss. Every patient is unique, and the choice of the medication depends on the patient. Getting a consult from an endocrinologist/diabetes specialist is a very important step. In our diabetes practice, we assess patients, understand their values and priorities. When weight loss is a priority, we discuss the potential use of these agents. If the patient is eligible and suitable for these agents, we prescribe and follow with the patient closely. If there is an insurance denial, we always try to negotiate with insurance to get the best possible alternative or appeal the decision.
For any further questions, you can call us anytime at 1-800-644-3963.
Ahmet Ergin, MD, CDE, ECNU
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