The Biggest News in Diabetes Technology and Drugs: Highlights from ADA 2021

By Eliza Skoler, Matthew Garza, Julia Kenney, Arvind Sommi, Andrew Briskin

The American Diabetes Association's 81st Scientific Sessions brought together great minds in diabetes for exciting news and discussions. Check out highlights from the largest conference in diabetes, including automated insulin delivery, continuous glucose monitoring, extremely promising drugs in development, and more.

We are expanding this year’s virtual ADA Scientific Sessions with our extended coverage of the conference – and what an event it was! This year’s conference covered so many important topics and lots of important research results were presented which highlighted everything from how the use of diabetes technology can lead to major Time in Range improvements to a host of new medications that lead to dramatic weight loss and A1C reduction.

Click to read our complete coverage from day one here and our coverage from days two and three here, or jump down to a particular section:

Technology

• Omnipod 5 AID system is safe and effective for people with type 1 diabetes of all ages

• New results on Medtronic’s Extended-Wear Infusion Set

• Dexcom G6 CGM drops A1C from 10.1% to 7.1% in people with type 2 diabetes

• Control-IQ leads to major Time in Range increases in older adults with type 1 diabetes

• Onduo’s virtual type 2 diabetes management program lowers A1C

• First look at real world data on the MiniMed 770G AID system

• CamAPS improves Time in Range in pediatric trial

• New analysis compares FreeStyle Libre and Dexcom G5 and G6 CGMs

Diabetes Therapies

• Full Results from SURPASS Trials Show Tirzepatide is Effective for Type 2 Diabetes

• Semaglutide STEP trials show impressive weight loss results

• Higher dose semaglutide leads to stronger A1C reductions and weight loss for people with type 2 diabetes

• Therapies for type 2 diabetes – early results of the GRADE Study

• Once-weekly GLP-1 drug may help youth with type 2 diabetes

• Inhaled insulin shows positive results in people with type 1 and type 2 diabetes

• Type 1 cures: Innovations in beta cell replacement therapy

• New GLP-1/glucagon combination medication shows impressive Time in Range and weight loss results

• GLP-1 medication efpeglenatide finds success in people with type 2 and heart or kidney disease

Other Coverage

• Treating diabetes and chronic kidney disease

• Aiming for balance: type 1 diabetes and exercise management

Diabetes Technology Leads to Major Improvements in Time in Range and A1C

The realm of diabetes technology is quickly expanding and improving – with the latest generation of continuous glucose monitors (CGM) and automated insulin delivery (AID) systems leading to major improvements in Time in Range and A1C. At the conference this year, researchers presented data showing how technology, such as the Dexcom G6, Omnipod 5, Control-IQ, and the CamAPS AID system can be used to help people spend more Time in Range.

Dexcom G6 drops A1C from 10.1% to 7.1% in people with type 2 diabetes

Dr. Thomas Grace (Blanchard Valley Diabetes Center) read out results from a six-month study that assessed the effect of Dexcom G6 use among people with type 2 diabetes on basal insulin-only, other glucose-lowering medications, or diet and exercise. The study included 38 participants with an average A1C of 10.1% (and all participants had values above 7.5%), Time in Range of 57%, BMI of 36 kg/m2, average age of 55 years, who had lived with diabetes for 14 years on average, and typically completed fewer than three fingerstick tests per day. Participants received CGM training from the clinic staff and attended three- and six-month clinic visits to review data and adjust medications as needed.

After six months, the data showed:

• Time in Range (70-180 mg/dL): increased by 3.6 hours per day to 72%.

• Time in hyperglycemia (above 180 mg/dl): fell 3.6 hours per day, from 43% to 28%. People also spent two fewer hours per day in severe hyperglycemia (above 250 mg/dL).

• A1C reduction: A1C went down to 7.1% (baseline 10.1%). This was seen among people using one, two, or more medications.

CamAPS improves Time in Range in pediatric trial

Dr. Julia Fuchs from the University of Cambridge shared data from a clinical trial on the CamAPS FX system in adolescents and children (ages 6 to 18) with type 1 diabetes. CamAPS FX is CamDiab’s hybrid closed loop system that combines an Android phone app, a Dexcom G6 CGM, and either the SOOIL Dana Diabecare RS pump or the Dana-i-pump. It adjusts insulin delivery every eight to twelve minutes according to a person’s needs and behaviors throughout the day, aiming for a glucose level of 105 mg/dL. At the start of the trial, the 46 participants were on standard insulin pump therapy and the majority were currently using or had used a CGM in the past – participants were randomly assigned to use either the CamAPS FX system or continue standard pump therapy for six months.

Data were reported as a change from baseline, though baseline values were not provided. After six months, those using the CamAPS FX system:

• Time in Range (TIR) : Spent on average 3.6 more hours per day in range, reaching 68%.

• A1C: Reduced A1C by 1.1%, dropping from 7.9% at baseline to 6.8%.

• Time above Range (glucose levels above 180 mg/dL): Fell by 4.4 hours per day, to 24%.

• Had a low frequency time spent in severe hypoglycemia and no instances of diabetic ketoacidosis (DKA).

These results are generally in line with what we’ve seen from other pediatric AID trials, though CamAPS FX is currently only approved in Europe.

New analysis compares FreeStyle Libre and Dexcom G5 and G6 CGMs

Dr. Eden Miller presented data showing nearly identical A1C reductions in people with type 1 and type 2 diabetes after starting to use continuous glucose monitoring (CGM), regardless of the device brand. The retrospective study looked at the electronic health records of 348 people with type 1 diabetes and 330 people with type 2 diabetes who all took rapid-acting insulin and had a baseline A1C above 7% when they began using either Abbott’s Freestyle Libre or Dexcom’s G5 or G6 CGM (the G5 CGM is an older model that is not widely used anymore).

Note: the Dexcom data below was not split up to show differences between the older G5 and the more advanced G6 sensors.

People with type 1 diabetes:

	Dexcom	Freestyle Libre
Number of people overall	116	232
A1C at baseline	8.5%	8.6%
Change in A1C after six months	-0.35%	-0.37%
Number of people with A1C above 8%	70	140
A1C at baseline for people with A1C above 8%	9.2%	9.3%
Change in A1C after six months	-0.6%	-0.7%

People with type 2 diabetes:

	Dexcom	Freestyle Libre
Number of people overall	110	220
A1C at baseline	9.0%	9.1%
Change in A1C after six months	-0.73%	-0.79%
Number of people with A1C above 8%	71	142
A1C at baseline for people with A1C above 8%	9.0%	9.1%
Change in A1C after six months	-0.8%	-0.8%

Dr. Irl Hirsch from the University of Washington did a similar analysis, comparing the rates of acute diabetes events (emergency high or low blood sugars) for each brand of CGM. Looking at the electronic health record data from 3,564 people with type 1 diabetes and 3,930 people with type 2 diabetes showed that the rate of acute events (high and low glucose emergencies) was nearly the same after six months of using either FreeStyle Libre or Dexcom CGMs: 6% among those with type 1 using Freestyle Libre, 5% among those with type 1 using Dexcom and 4% among those with type 2 using either device. 

Together, the data from these two studies show that both major brands of CGM benefit people with type 1 or type 2 diabetes – and are particularly helpful for people who start with a higher A1C level.

GRADE Study Shows GLP-1 Medication Rising to the Top

One of the most interesting collections of early data presented this year at ADA were results from study called the GRADE study. This was one of the first and only studies with a diverse participant population that directly compared diabetes therapies (in this case insulin, a DPP-4 inhibitor, a sulfonylurea, and a GLP-1 receptor agonist). The GLP-1 medication (liraglutide, also known as Victoza or Saxenda) really rose to the top amongst the group with impressive A1C, weight loss, and cardioprotective results.

Therapies for type 2 diabetes – early results of the GRADE Study

How can we help more people with type 2 diabetes effectively reach their A1C goals? That’s what the Glycemia Reduction Approaches in Diabetes Comparative Effectiveness (GRADE) Study is evaluating. Over nearly three decades, eight new classes of type 2 diabetes therapies have been approved, but there has not been adequate research comparing their relative efficacies and how they work as next medications after monotherapy. GRADE is studying four therapies – basal insulin (glargine also known as Lantus), DPP-4 inhibitor (sitagliptin also known as Janivia), sulfonylurea or SFU (glimepiride), and GLP-1 (liraglutide also known as Victoza) – for use with metformin in more than 5,000 people with type 2 diabetes.

In addition to A1C, researchers are looking at a variety of measures, including diabetes complications and side effects. Importantly, the study recruited a diverse population (20% of participants were Black, 4% Asian, 3% Native American/Alaskan Native, and 18% Hispanic/Latino). At baseline, the participants had an average A1C of 7.5%, BMI of 34, blood pressure of 128/77 mmHg, eGFR of 95 mL/min/1.73m², a diabetes duration of up to ten years, and took 1,944 mg of metformin per day. Preliminary results show:

• A1C. GLP-1 agonist liraglutide (Victoza) and insulin glargine (Lantus) were most effective at keeping participants’ A1C levels below 7%. This was followed by the SFU, glimepiride, and DPP-4 inhibitor sitagliptin (Januvia). 

• Complications.

  • There was no difference in the prevalence of microvascular complications among the four treatment groups, though some participants did develop microvascular complications during the study.

  • The GLP-1 drug resulted in lower rates of heart disease compared to the other therapies. Based on preliminary data from an average follow up of five years, the percentage of participants who developed any cardiovascular disease was 5.8% for those on liraglutide, 7.6% for glargine, 8.0% for glimepiride, and 8.6% for sitagliptin.

• Hypoglycemia. Hypoglycemia was infrequent across all four treatment groups. There was a slightly higher rate of hypoglycemia in the sulfonylurea group (2.3%, which was not statistically significant).

• Weight loss. People in the DPP-4 inhibitor and GLP-1 treatment groups lost significantly more weight than the other participants. Participants in the insulin glargine group did not gain weight but those taking the SFU did gain weight.

Researchers hope that by investigating the effectiveness of these different therapies across diverse populations, diabetes medicines can be better personalized for each individual with type 2 diabetes. Understanding how these therapies compare in reducing A1C, preventing microvascular and macrovascular complications, and improving quality of life can help people with diabetes and their healthcare professionals make more informed treatment decisions. In addition, this trial is about progressing to new therapies at the right time in addition to metformin. GRADE started recruiting in 2013 and finished data collection in 2021 – we are eager to see more results of the GRADE Study, particularly in the CGM sub-study.

New Diabetes Medications Show Dramatic Weight Loss and A1C Reductions

One of the stars of the show at this year’s ADA Scientific Sessions was a whole host of drugs, headlined by semaglutide (which you may know by its brand names Ozempic, Rybelsus, or its new name Wegovy which was just approved as a weight loss drug) that have led to truly dramatic weight loss and A1C reductions. Read more on semaglutide, and newer drugs tirzepatide, cotadutide, and efpeglenatide below.

Semaglutide STEP trials show impressive weight loss results

Exciting results were shared from the STEP trials testing the use of semaglutide in people with obesity or excess weight. The results from these trials led to FDA approval of Wegovy just a few weeks ago. Wegovy is a 2.4 mg dose of the once-weekly GLP-1 agonist semaglutide that was approved for weight loss in people with excess weight or obesity.  The same medication is used for treating type 2 diabetes, known as Ozempic (weekly injection of 0.5 or 1.0 mg compared to the 2.4 mg dose in Wegovy) or Rybelsus (an oral pill).

Professor Melanie Davies from the University of Leicester explained that the higher dosage of semaglutide now approved for weight management helps to reduce appetite and cravings, as well as energy intake, increases feelings of fullness, and ultimately leads to more weight loss (than other GLP-1s drugs) and lowered risk of heart disease.

Dr. Robert Kushner from Northwestern University discussed results from the four main STEP trials. There were 4,700 participants across all four trials. Over 68 weeks, researchers evaluated the percentage of weight lost among the participants. Throughout the trials, the main side effect was nausea (which was expected) and the medication was determined to be safe.

Trial	Baseline Characteristics	Results
STEP 1	This trial was the basic trial in people with obesity or excess weight Average BMI of 37.9. Given semaglutide 2.4 mg dose	Participants receiving semaglutide showed an average weight reduction of 14.9% (compared to 2.4% in the placebo group). Of those on semaglutide, 86.4% experienced at least a 5% weight reduction, compared to 31.5% who achieved this target in the placebo group.
STEP 2	This trial was in people with type 2 diabetes. Average BMI of 35.7 and average A1C of 8.1%. Two doses of semaglutide (1.0 mg and 2.4 mg) were tested.	In the group receiving semaglutide (2.4 mg), participants had an average weight reduction of 9.6%, compared to 7.0% in the semaglutide (1.0 mg) group, and 3.4% in the placebo group. Those receiving semaglutide (2.4 mg) reduced their A1C by 1.6 percentage points, compared to 1.5 percentage points in the semaglutide (1.0 mg) group, and 0.4 percentage points in the placebo group. Weight loss and A1C were associated: the more weight lost, the more A1C decreased.
STEP 3	This trial included eight weeks of a low-calorie diet followed by intensive behavioral therapy in people with obesity or excess weight. Average BMI of 38.0. Given semaglutide 2.4 mg dose	In the group receiving semaglutide, participants had an average weight reduction of 16.0% (compared to 5.7% in the placebo group). Though the lifestyle counseling helped participants lose weight slightly faster, by week 68 overall weight loss was similar to results seen in the STEP 1 trial.
STEP 4	Participants with obesity or excess weigh took semaglutide for the first 20 weeks, and were then randomly assigned to continue the treatment or switch to a placebo. Average BMI of 38.3. Given semaglutide 2.4 mg dose	At week 20 the average weight reduction was 10.6% for everyone. The group that continued on semaglutide ended up with a total weight reduction of 17.7% by week 68, while the group that was switched to the placebo gained weight and ended up with a final weight reduction of 5.4%.

Professor John Wilding from the University of Liverpool spoke about the health outcomes of these trials, specifically for people with prediabetes. He stressed that semaglutide (at a lower dose of 1.0 mg and known as Ozempic for treating diabetes) helps people reduce their total body fat percentage which can lead to improvements in blood pressure, cholesterol and triglycerides, inflammation, A1C level, and waist circumference. In STEP 2, semaglutide helped 29% of participants with diabetes reduce the number of oral glucose-lowering medications they were taking following the trial. In STEP 1, of the individuals given semaglutide, the number of people with prediabetes decreased (from 45% to 16%) and the number of people with “normal” glucose levels increased (55% to 84%). These results suggest that semaglutide may be helpful for preventing diabetes.

Finally, Dr. Lee Kaplan from the Massachusetts General Hospital discussed the implications of semaglutide for treating obesity and excess weight. The drug provides healthcare professionals with another option for helping people with diabetes, obesity, or excess weight, and could be used in combination with other medications to help manage comorbidities. Dr. Kaplan finished with a powerful message about the importance of semaglutide, saying, “Obesity needs to be recognized as a disease in its own right, as well as a risk factor for numerous diseases. Equitable access to obesity treatment [such as semaglutide] needs to be broadened, and healthcare providers need to take more responsibility for the control of this serious problem.”

Higher dose semaglutide leads to stronger A1C reductions and weight loss for people with type 2 diabetes

Could higher doses of semaglutide be even more helpful for people with diabetes? Dr. Juan Frias presented the results from the SUSTAIN FORTE trial which compared two different doses of semaglutide (a GLP-1 agonist medication) in almost 1000 people with type 2 diabetes. Participants were given either 1.0 mg or 2.0 mg doses. Only the 1.0 mg dose is currently indicated for people with diabetes; however, a 2.4 mg dose of semaglutide was recently approved by the FDA for weight loss in people with obesity or excess weight.

There were 481 total participants in the semaglutide 1.0 mg group, with an average diabetes duration of about ten years, a baseline A1C of 8.8%, and a BMI of 34.4. There were 480 participants in the semaglutide 2.0 mg group, with an average diabetes duration of about nine years, a baseline A1C of 8.9%, and a BMI of 34.8. After 40 weeks:

• Participants taking the 2.0 mg dose saw a 2.2 percentage point reduction in A1C (from 8.9% at baseline). The semaglutide 1.0 mg group saw a 1.9 percentage point reduction A1C.

• About half of participants (52%) in the semaglutide 2.0 mg group achieved an A1C of 6.5% or lower, compared to 39% in the semaglutide 1.0 mg group.

• In terms of weight loss, 59% of participants experienced at least 5% weight loss on semaglutide 2.0 mg, compared to 51% of participants on semaglutide 1.0 mg. And, 28% of people on semaglutide 2.0 mg experienced a weight loss of at least 10% (compared to 23% on semaglutide 1.0 mg).

Higher dose semaglutide is currently under FDA review. Another dosing option for healthcare professionals to prescribe to help manage both diabetes and weight would be beneficial – especially given the results seen with the higher dose.

Combination Drug Tirzepatide Dramatically Lowers Weight and A1C

The eagerly-anticipated, full results of the phase 3 SURPASS trials were shared at ADA 2021. Earlier this year, exciting early results from several trials of tirzepatide showed that the new drug can lead to a sizable A1C reduction, significant weight loss, and less hypoglycemia among people with type 2 diabetes. Tirzepatide is a once-weekly injectable medication. This new glucose-lowering therapy is called a “dual GIP and GLP-1 receptor agonist” and is currently in development to help people manage type 2 diabetes. Read our highlight on the full results from the SURPASS trials here.

New GLP-1/glucagon combination medication shows impressive Time in Range and weight loss results

A new drug in development shows potential for helping people with type 2 diabetes and chronic kidney disease. Although it’s in the very early stages of development, we aim to inform you on all the interesting new medications coming through the pipeline. New data from a collection of trials for Astrazeneca’s cotadutide – a GLP-1/glucagon receptor dual agonist – showed impressive early results for type 2 diabetes management in terms of Time in Range and weight loss. This randomized, controlled included 41 people with type 2 diabetes (baseline A1C levels between 6.5% to 10.5%), stage 3 chronic kidney disease (CKD, with an eGFR between 0-59 mL/min/1.73 m²), and BMI between 25 to 45, who took insulin or oral glucose-lowering drugs. Half of the participants received a placebo while the other half received cotadutide for 32 days. Results from this short, small trial showed:

• Cotadutide led to a 27% reduction in plasma glucose levels (from baseline) during the four hours after a meal, compared to a 3.7% glucose level increase in the placebo group.

• Time in Range (TIR) increased by almost 15 percentage points from baseline in the cotadutide group – that’s an increase of 3.5 hours per day. TIR in the placebo group actually decreased by 21 percentage points, which may be caused by a number of factors during the short trial.

• People taking cotadutide lost an average of 3.7% of their baseline body weight, compared to a weight loss of 0.2% with the placebo.

• With cotadutide, total daily insulin decreased in people receiving more than 20 U baseline dose. The 14 participants in this subset showed a 35.2% reduction in dose.

• Early evidence suggests that cotadutide may also help the kidneys. In 18 participants with micro- or macroalbuminuria, their UACR (a measure of kidney damage) was reduced by 51%, compared to the placebo group.

• The safety profile was similar to other GLP-1 receptor agonist drugs; the main side effects were gastrointestinal.

Dr. Rajna Golubic presented findings from a separate exploratory trial of cotadutide in 28 people with type 2 diabetes and obesity or excess weight. Participants had an A1C less than 8% and a BMI between 28 and 40. Those given cotadutide saw significantly greater weight loss (4% weight loss compared to 1.5% in the placebo group). Dr. Golubic suggested that this weight loss may have been caused by reduced energy intake (participants given cotadutide ate less than the placebo group).

Cotadutide is currently being studied in a small clinical trial against semaglutide to compare how each drug affects chronic kidney disease, and it is also being evaluated in another trial to see how cotadutide affects people with liver disease (specifically NASH, nonalcoholic steatohepatitis). These early trials will help inform an eventual large-scale trial. Given the seriousness of kidney disease and the lack of medications for treating NASH, a new medication that could help people with these conditions brings a lot of hope. We will keep our readers updated on results from these trials as they come.

GLP-1 medication efpeglenatide could help people with type 2 and heart or kidney disease

The AMPLITUDE-O trial looked into the efficacy of efpeglenatide (a new GLP-1 agonist medication in development) in preventing major adverse cardiovascular outcomes (MACE), such as heart attacks, in people with type 2 diabetes at high risk for these heart events. More than 4,000 participants from around the world were randomly assigned to receive either efpeglenatide (a 4 mg or 6 mg dose) or placebo, and followed for about two years. At baseline, participants had an average age of 64.5 years, diabetes duration of 15.4 years, and A1C of 8.9%. Additionally, 90% of people had prior cardiovascular disease, 63% were taking insulin, and 15% were taking an SGLT-2 inhibitor.

• Treatment with efpeglenatide reduced average A1C by 1.2 percentage points, weight by 5.7 pounds (2.6 kilos), BMI by 0.92, and blood pressure, when compared to the placebo. The drug was found to be safe but led to a moderate increase in heart rate, which is consistent with most other GLP-1 medications. The most common side effects were gastrointestinal.

• Efpeglenatide led to positive heart health outcomes: a significant 27% relative risk reduction for the primary outcome of MACE (a first time, non-fatal heart attack, stroke, or death from cardiovascular disease). The benefits of the drug were evident within the first three months of treatment, and dose-dependent – the 6 mg dose reduced risk more than the 4 mg dose.

• Efpeglenatide also benefited the kidneys, resulting in a 32% relative risk reduction in several negative kidney outcomes (such as new macroalbuminuria, a decrease in eGFR, and renal replacement therapy).

These positive results could lead efpeglenatide to eventually become another type 2 diabetes medication that also protects the heart and kidneys and shows even more certainty that GLP-1s do indeed protect our hearts – a win for people with diabetes.

Experts Speak to the Importance of Exercising Safely

Exercise is so important for keeping everyone healthy, but for people with diabetes, navigating exercise in a safe and beneficial way can be a challenge. At the ADA conference this year, experts reiterated some of the tips and tricks for exercising with the goal of keeping your blood glucose levels in range.

Aiming for Balance: Type 1 Diabetes and Exercise Management

Experts on exercise, nutrition, and type 1 diabetes discussed the latest strategies and recommendations for blood glucose management during physical activity. Endocrinologist Dr. Ian Gallen from the UK’s National Health Service shared the effects of different types of exercise on blood glucose:

• Aerobic exercise causes blood glucose to fall, while intense anaerobic exercise can cause a rise in glucose levels.

• Weight and resistance training can cause an initial rise in glucose, but repetition over time can cause a decrease.

• Altering the timing and order of exercises can help stabilize blood glucose levels over long periods of physical activity.

• Careful carbohydrate consumption before, during, and after exercise, along with the use of short-acting mealtime insulin, is crucial to avoid low blood sugar after exercise.

It’s important to remember that different people’s glucose levels can respond differently to exercise. Always make sure that you have everything you need in case of an emergency and talk to your healthcare team to come up with an exercise plan.

How much should you be exercising? According to the American Diabetes Association, adults with type 1 should engage in at least 150 minutes (or two and a half hours) of moderate to vigorous exercise per week, with no more than two consecutive days without activity. However, only about 30% of people with type 1 diabetes meet this goal. Here are some strategies for people with diabetes to improve glucose management while exercising:

• Measure blood glucose levels prior to exercise.

• Start exercise when glucose levels are within the target range of 125-180 mg/dL. To adjust your glucose levels to the higher end of this healthy range, you can eat 10g to 20g of glucose, depending on your target.

• Continuous glucose monitors (CGM) can help people understand variations in blood glucose while exercising.

• Have a goal of spending more than 70% time in your target glucose range throughout periods of physical activity.

To learn more about exercising with diabetes, click here and read “Want to Stay Active or Get More Exercise? Strategies for Glucose Management.”

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