Insulin is a hormone made by the pancreas that allows blood sugar to enter cells and provide fuel.The body of someone with type 2 diabetes either does
Insulin is a hormone made by the pancreas that allows blood sugar to enter cells and provide fuel.
The body of someone with type 2 diabetes either does not produce enough insulin or does not respond to insulin in the way that it should.
Uncontrolled high blood sugar may lead to severe complications, such as
Different types of medication can reduce blood sugar in people with type 2 diabetes. Some examples include:
The 2022 American Diabetes Association guidelines say that the first-line treatment is usually metformin, a biguanide, and
But the initial treatment choice also depends on the presence or risk of other health conditions, including heart failure, coronary artery disease, or chronic kidney disease. A doctor also considers the person’s preferences, their access to medication, and its cost, effectiveness, side effects, and impact on weight.
Often, combination therapy, involving two or more drugs, is necessary to keep blood sugar within the appropriate range in order to delay or prevent
But some people with type 2 diabetes cannot reach blood sugar goals with currently available combination therapies.
The need for new, more effective treatment options forms the basis of the FDA’s approval of tirzepatide, a novel drug for type 2 diabetes.
Tirzepatide is the first drug in a new class of diabetes medications. It is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist.
GLP-1 and GIP are gut hormones called incretins, and the intestines
GLP-1 increases the release of insulin from the pancreas. It also reduces levels of glucagon, a hormone that prevents blood sugar from decreasing too much.
Another role of GLP-1 is increasing the number and volume of beta cells in the pancreas. It also promotes a feeling of fullness by delaying stomach emptying and controlling appetite in the brain.
Like GLP-1, GIP increases insulin release. It also improves beta cell production and decreases beta cell destruction. Additionally, GIP reduces fat accumulation, increases bone formation, increases glucagon production, and reduces acid secretion in the stomach.
People with type 2 diabetes do not respond as strongly to incretin hormones as other people. Tirzepatide addresses this deficit by activating the GLP-1 and GIP receptors in the body.
In a video, Dr. Carol Wysham, a clinical endocrinologist at the Rockwood Clinic, in Spokane, WA, and a clinical professor of medicine at the University of Washington, speaks about the dual GLP-1 and GIP actions of tirzepatide. She explains:
“They both have somewhat separate activities, but they have [greater activities in combination], causing insulin secretion, improving glucose tolerance, and decreasing body weight.”
In a clinical trial called
The participants received one of three tirzepatide dosages: 5 milligrams (mg), 10 mg, or 15 mg, or a placebo injection under the skin once weekly for 40 weeks.
The study showed that participants taking tirzepatide had significantly greater reductions in A1C, a measure of blood sugar, than the placebo group. A1C dropped by 1.87 to 2.07%, depending on the dosage.
Also, compared with the placebo group, participants taking tirzepatide lost more weight: 7 to 9.5 kilograms (kg), or 15.4 to 20.9 pounds (lb).
In SURPASS-2 trials, participants with type 2 diabetes received the same dosages of tirzepatide as in the previous trial or a 1-mg dosage of semaglutide once weekly for 40 weeks. Semaglutide is an FDA-approved GLP-1 agonist used to treat type 2 diabetes.
Tirzepatide reduced A1C from 2.01 to 2.3%, depending on dosage, whereas semaglutide reduced it by 1.86%.
The trial also reported significantly greater weight reductions in the tirzepatide group, compared with the semaglutide group. In the former, weight loss ranged from 1.9 kg (4.2 lb) to 5.5 kg (12.1 lb).
The study recruited people with type 2 diabetes who had not previously used insulin and did not respond adequately to treatment with metformin alone or in combination with SGLT2 inhibitors.
After 52 weeks, participants receiving tirzepatide had significantly greater reductions in A1C, compared with those receiving insulin degludec. The first group also experienced significantly greater weight losses.
In the next trial, called
These participants were already using one or more diabetes drugs and had inadequate blood glucose control at the beginning of the study.
Participants received a weekly dose of tirzepatide or insulin glargine, another injectable diabetes drug, for 52 weeks.
Once again, participants who received tirzepatide achieved better A1C reductions and weight loss than those who received insulin glargine.
The SURPASS-5 trial evaluated tirzepatide as an add-on drug for people with type 2 diabetes who were already taking insulin glargine, with or without metformin. The trial measured A1C and weight reduction in participants receiving a placebo and others receiving tirzepatide once a week in addition to their previous treatment for 40 weeks.
Those taking tirzepatide as an add-on treatment achieved greater A1C reductions and weight loss than those who received a placebo.
Dr. Laurie A. Kane, an endocrinologist at Providence Saint John’s Health Center, in Los Angeles, CA, spoke to Medical News Today about tirzepatide. She explained:
“Tirzepatide is unique because it’s combining a GLP-1 plus a GIP agent in one injection, and the efficacy we’re seeing in glucose-lowering plus weight [loss] is beyond anything we have available right now. […] A lot of the agents on the market give us about a 1% lowering of A1C or less, depending on A1C levels when starting treatment.”
In the study participants, the most commonly reported side effects of tirzepatide were nausea, diarrhea, vomiting, and constipation. Severe low blood sugar also occurred, but infrequently.
Dr. Wysham explains: “The gastrointestinal side effects from tirzepatide are very similar to […] the GLP-1 agents. […] Much like the studies with GLP-1 receptor agonists, the nausea was greatest at the initiation of the dose and with increasing doses, and then tended to [decrease] with time.”
Researchers continue to investigate the long-term safety of tirzepatide and its potential effects on cardiovascular outcomes, such as heart attack, stroke, and cardiovascular death.
Dr. Kane commented: “As long as we’re using agents that don’t have any hypoglycemic risk, which is the case with [tirzepatide], aiming for a lower A1C is going to put [people with type 2 diabetes] in a better position for preventing long-term complications. A1C lowering down to 5.7% is pretty incredible.”
She added, “It’s probably going to be the cost of the agent and the coverage by insurance that will be the obstacle in some cases, so we’ll have to wait and see how that plays out.”
MNT also spoke with Dr. Robert Gabbay, the chief science and medical officer at the American Diabetes Association. Looking to the future, he is interested to learn whether the drug might also help address complications related to type 2 diabetes, he said:
“We look forward to learning whether tirzepatide can provide any benefit in cardiovascular disease, NASH [a form of nonalcoholic fatty liver disease], and other complications, such as retinopathy, nephropathy, and neuropathy.”