New Drug Tirzepatide Shows Extraordinary Results For Obesity and Type 2 Diabetes
By Andrew Briskin
Clinical trial results published by Lilly show that Tirzepatide could potentially be one of the most effective drugs ever developed for weight loss. Experts discuss these results and more at the ATTD 2022 conference in Barcelona, Spain.
Researchers at ATTD 2022 announced the latest study results on tirzepatide, further strengthening the evidence for its success in people with either obesity or type 2 diabetes, or those with both conditions, to improve weight loss and glucose management.
Tirzepatide is known as a “dual agonist” or a “dual GIP and GLP-1 receptor agonist.” It is similar to GLP-1 receptor agonists, which have been shown to lower glucose levels, lead to weight loss, and lower the risk of heart disease, but then adds a GIP agonist.
The new study, SURMOUNT-1, for which Lilly released preliminary results this week at ATTD, looked at the impact tirzepatide (at various doses) had on body weight, when combined with a low-calorie diet and increased exercise.
Those taking Tirzepatide at the lowest dose (5 mg) had an average of 15.0% loss in body weight over the course of the trial.
For groups taking higher doses of 10 mg and 15 mg, weight loss went up to 19.5% and 20.9%, respectively.
In this final group taking 15 mg, 63% of people achieved weight loss of over 20% of their body weight.
“We always hear about new therapies that will ‘change everything’, but nothing really changes,” said Dr. Julio Rosenstock, director of the Dallas Diabetes Research Center in Dallas, Texas, who presented the new findings. “I think [Tirzepatide] is a true treatment paradigm change for type 2 diabetes.”
Experts on the ATTD panel said these latest results echoed and built upon the astonishing results of the 2021 SURPASS trials, a group of five large phase 3 clinical trials that showed striking reductions in A1C and weight. These prior trials compared the impact of tirzepatide at three different doses (5, 10, and 15 mg) to a GLP-1 receptor agonist, multiple once-daily insulins, and diet and exercise alone.
More details on those results can be found in our article: "Tirzepatide Dramatically Lowers Weight and A1C."
The new results added to the already strong evidence that tirzepatide can have a significant positive impact on insulin resistance, non-alcoholic fatty liver disease (NAFLD), and on daily glucose profiles, as measured by Time in Range (TIR) using a continuous glucose monitor (CGM).
Tirzepatide and insulin resistance
Insulin resistance, one of the main characteristics of type 2 diabetes, means your body’s cells cannot use insulin properly in order to take in glucose from the blood for energy. Earlier GLP-1 drugs such as semaglutide (sold under brand names Ozempic, Wegovy, and Rybelsus) have been shown to decrease insulin resistance, while also leading to weight loss and A1C improvements.
Andrea Mari, research scientist at the Institute of Neuroscience, National Research council in Padova, Italy, discussed study results comparing the effects of tirzepatide and semaglutide on weight loss, A1C, and overall beta cell function (the insulin-producing cells in your pancreas). Not only did tirzepatide lead to greater A1C reduction and weight loss over the 28 week trial, it also doubled the improvement in insulin sensitivity compared to semaglutide.
“The known effects of GLP-1s on beta cell function, weight loss, and insulin sensitivity are greatly potentiated with tirzepatide,” Mari said, meaning that tirzepatide had even more significant effects than GLP-1s. “This can largely reverse the main metabolic defects underlying type 2 diabetes.”
Tirzepatide and liver disease
Amalia Gastaldelli, research director of the Cardiometabolic Risk Laboratory at the Institute of Clinical Physiology in Pisa, Italy, explained that non-alcoholic fatty liver disease (NAFLD) is significantly more common among people with type 2 diabetes. In addition, decreases in fat levels in the liver are directly associated with improvements in insulin sensitivity and overall metabolism in people with type 2 diabetes.
As an addition to the SURPASS-3 trial, researchers compared the effects of tirzepatide to degludec, a once-daily insulin, on liver fat in 296 people with type 2 diabetes. Even at its lowest dose, tirzepatide led to shocking improvements in liver fat.
The figure below shows an MRI scan of an individual with type 2 diabetes on a 5 mg dose of tirzepatide for 52 weeks. Red and yellow represent the presence of fat, and after 52 weeks, liver fat content went from 27.3% to just 2.6%.
Tirzeptide and daily glucose management
Dr. Tadej Battelino, head of the Department of Endocrinology, Diabetes & Metabolism at University of Ljubljana, Slovenia, described how tirzepatide also improved daily glucose profiles for people with type 2 diabetes, as measured by Time in Tighter Range (TITR), or percent of time spent within a tight glucose range between 70 and 140 mg/dL.
Battelino reported on an addition to the SURPASS-3 study, comparing the effects of once-weekly tirzepatide dosing and once-daily insulin degludec on TITR. At the end of the 52-week study, those taking tirzepatide had an average TITR of 73%, compared to only 48% for those taking degludec. This is compared to starting averages of 23% and 22%, respectively.
Perhaps even more astonishing, however, were two individual case studies that Battelino highlighted. The first was a 59-year-old man, with a BMI of 27 and TITR (70-140 mg/dl) of about 5%. After 52 weeks on a 5 mg dose of tirzepatide, TITR increased to over 95%, while A1C was reduced by 3.6 percentage points and weight loss over 50 lbs.
In another case, a 61-year-old individual had obesity and type 2 diabetes, was taking metformin, had an A1C of 10.1%, and a TITR of less than 1% each day. After 52 weeks of taking a 15 mg dose of tirzepatide, TITR skyrocketed to over 98%, A1C fell by over 5 percentage points, and they experienced a weight loss of around 50 pounds.
Battelino praised the use of CGM in these studies, in order to personalize care and track the day-to-day impact of tirzepatide.
“CGM is so critical as an intermittent measure to determine if therapies are sufficient for the individual,” he said.
Tirzepatide and type 1 diabetes
So far, all clinical trials for tirzepatide have only included people with type 2 diabetes or obesity, and the drug is not currently intended for people with type 1 diabetes. However, given that some people with type 1 can also develop resistance to insulin and may benefit from weight loss , experts emphasized that they would like to see a study of tirzepatide in appropriate people with type 1 diabetes in the near future.
Latest clinical trial results: Type 2 diabetes remission and treatment for obesity
Rosenstock concluded the session by announcing the exciting preliminary results of Lilly’s SURMOUNT-1, a 72-week study including 2,539 participants with excess weight or obesity who did not have diabetes, which showed significant weight loss at all three dose levels..
Rosenstock said he was excited about the clinical study results and the growing evidence that tirzepatide had the potential to support type 2 diabetes remission.
Pointing to the 2021 SURPASS trials, Rosenstock noted that half of people taking the highest dose of tirzepatide (15 mg) in those trials achieved enough weight loss and glucose level stability to potentially achieve remission. “If you lose 10 to 15 kilograms, you have a much greater chance of remission,” he said.
Tirzepatide led to an average 2.0% A1C reduction across all SURPASS trials, and all groups taking a 15 mg dose of tirzepatide had an average A1C below 6%. “That’s unheard of,” Rosenstock exclaimed. “You simply don’t see that!”
Mentioning the many additional benefits that could potentially come from tirzepatide but have not yet been studied in trials, Rosenstock said he suspected that tirzepatide could show a cardiovascular benefit as well.