People with Type 1 and Type 2 diabetes who are already on insulin but are looking for better readings can often benefit from taking another medication with their insulin. Consider the benefits and drawbacks of these meds that can assist insulin before you try them.
Symlin (pramlinitide) replaces amylin, a hormone normally secreted by the same cells that make insulin. In Type 1 diabetes, levels of both insulin and amylin are very low or absent, while in Type 2 diabetes insulin and amylin levels are initially higher than normal and then fall off as beta cell activity is gradually lost over time. Like the GLP-1 agonists discussed below, Symlin slows digestion, minimizes glucagon secretion to reduce the amount of glucose the liver releases into the blood, and often reduces excess appetite.
- Significant reduction in post-meal glucose spikes
- May help those who are overweight lose a few pounds
- Often reduces the amount of insulin required per day
- OK with heart or liver problems, no known kidney problem
- Injected 2 to 3 times a day before meals and cannot be mixed in with insulin
- May cause nausea initially, less so when doses are gradually increased
- Hypoglycemia can occur if insulin doses are not reduced enough
- Can slow treatment of hypoglycemia with food because digestion is slowed
Byetta, Victoza, and Bydureon (GLP-1 agonists) are called incretins and have similar benefits to Symlin but for a different reason. GLP-1 agonists got their name because they mimic the effects of GLP-1, short for glucagon-like peptide-1, a special chemical messenger secreted by cells in the intestine when foods come in contact with the intestinal lining. Two incretins, GLP-1 and GIP, are responsible for as much as 70% of the insulin release that occurs after meals. The release of insulin is often reduced at the start of a meal in Type 2 diabetes, but interestingly, is often regained when insulin injections are used to treat Type 2. Insulin and GLP-1 provide complementary benefits in Type 2 diabetes. In both Type 1 and Type 2 diabetes, GLP-1 agonists typically suppress the excess glucagon production seen after meals, slow digestion, and decrease appetite.
- Decreases glucose variability for fewer ups and downs
- Lowers post-meal glucose levels with some lowering of fasting glucose levels
- Often causes weight loss
- Helps a functioning pancreas, as in Type 2, release a rapid burst of insulin when food is eaten
- Does not raise the risk of hypoglycemia unless insulin doses are excessive
- Can increase insulin secretion from the pancreas in Type 2 when the glucose is above normal
- May improve and preserve the health of the beta cell, lessening or eliminating the need to start or increase insulin in Type 2
- OK with liver or heart problem
- Must be taken by injection. Byetta (exenatide) twice daily, Victoza (liraglutide) once daily, and Bydureon (extended release exenatide) once a week. Cannot be mixed with insulin
- Not FDA approved for Type 1, although research studies show benefits
- Nausea or vomiting may occur at first, usually resolves
- People with gastrointestinal problems or kidney disease are not good candidates
- Responses to GLP-1 agonists vary widely from person to person
- Not used with moderate or severe kidney disease
Januvia, Tradjenta, Onglyza, and Nesina are a growing group of DPP-4 inhibitors. DPP-4 is a naturally occurring enzyme that rapidly breaks down GLP-1 and ends its action. The DPP-4 inhibitors block the effect of DPP-4, thus allowing the body’s own GLP-1 to stay active in the system and work much longer. DPP-4 inhibitors also raise a number of compounds besides GLP-1 that DPP-4 would normally break down. Thus, they do not work as “cleanly” as the GLP-1 agonists.
- Taken in pill form
- Lowers post-meal blood glucose levels, although not as well as GLP-1 agonists, with some lowering of fasting glucose levels
- Has minimal side effects
- In a 2011 study, Januvia allowed Type 1s to reduce insulin by 10%
- OK with heart or liver problem
- Not FDA approved for use with insulin
- Not FDA approved for Type 1
- Does not promote weight loss
- Glucose lowering impact is about half of that seen with GLP-1s
- Reduce dose with kidney problem
Invokana (canagliflozin) released in March, 2013, and Farxiga (dapagliflozin) released in January, 2014, are SGLT2 inhibitors. These meds increase the amount of glucose excreted through the kidneys into the urine. SGLT2, short for sodium-glucose transporter 2, normally helps the body reabsorb glucose molecules (fuel) from the urine that would otherwise be lost. However, when glucose levels are high in diabetes, this normally protective action is no longer helpful. SGLT2 inhibitors block the action of SGLT2 and increase the amount of glucose that the kidneys spill into the urine.
- Taken in pill form
- Lowers HbA1c and fasting glucose levels in Type 2’s
- May reduce body weight when glucose levels are often high
- May reduce systolic blood pressure
- Not FDA approved for use in Type 1 diabetes
- Increases frequency and amount of urination
- Increases the risk of urinary tract and genital infections, may increase kidney infections
- May cause hypoglycemia if insulin doses are not adjusted downward
An old drug derived from the lilac plant, metformin’s glucose-lowering effects were first noted in the 1920s. It became available in Canada in 1972 and was approved for use in the U.S. in 1994. Its primary action occurs in the liver where it reduces excess glucose production. This is important in Type 2 diabetes where insulin-resistance in many cells including those in the liver makes it harder to stop the liver’s production of excess and unwanted glucose.
Metformin comes in handy during the teen years when growth hormone (GH) levels are high. In teens with Type 1 diabetes, the liver’s glucose production becomes excessive due to higher growth hormone levels but also because the direct delivery of insulin from the pancreas to the liver is lost. In Type 2 diabetes glucose production rises because the liver like other organs has become resistant and insulin production is failing. GH production is highest in the early morning hours and is primarily responsible for the Dawn Phenomenon (high fasting glucose). Metformin stops much of this excess glucose production, lowers insulin requirements, and can make the teen years more enjoyable. Metformin also lowers insulin requirements in many adults with Type 1 and Type 2 diabetes.
- Taken in pill form twice a day or once a day with extended release form
- Lowers fasting glucose levels in Type 2 and in some with Type1 diabetes
- Mild weight loss in some
- Extended release form is less likely to cause nausea, heartburn, or diarrhea
- Not FDA approved for use in Type 1 diabetes
- May cause nausea, heartburn, or diarrhea in some (less likely when taken with food or with extended release form)
- May cause a rare but very severe disorder called lactic acidosis in people who have congestive heart failure or severe kidney disease (Metformin is not advised when the creatinine is over 1.4 in women or 1.5 in men.)
- Avoid with kidney, liver, or heart problems