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After demonstrating efficacy and safety as a weight loss agent in randomized clinical trials, a retrospective cohort study from a Mayo Clinic-led team is providing insight into the real-world effects of 2.4 mg semaglutide (Wegovy) for weight management.

With data from more than 150 patients treated at a referral center for weight management prescribed semaglutide for 3 months or more between January 1, 2021-March 15, 2022, results of the study suggest the mean weight loss achieved at 3 months was 5.9% of body weight, with this improving to 10.9% at 6 months and further analysis indicating more than 50% of semaglutide users achieving weight loss of 10% or more at 6 months.

“This study may be a stepping stone to demonstrating the effectiveness of semaglutide for patients aiming to lose weight. These results may support the applicability of semaglutide in a less controlled environment, as previously proven in RCTs,” wrote investigators.

With the US FDA’s approval of 2.4 mg semaglutide in June 2021 for chronic weight management in patients with overweight or obesity, the weekly GLP-1 receptor agonist became the first drug to receive such an approval in more than half a decade. Based on the results of the pivotal STEP program, the agent boasted a mean weight loss of 6% of body weight at 3 months and 12% of body weight at 28 weeks. Now, more than a year removed from FDA approval, investigators launched the current study citing a lack of retrospective studies assessing effectiveness of the increased doses of semaglutide outside of a clinical trial setting.

Designed as a retrospective review of electronic medical record data from individuals in the Mayo Clinic Health system using 1.7 mg or 2.4 mg semaglutide from January 1, 2021-March 15, 2022, the study’s primary endpoint of interest was the percentage of weight loss, with secondary endpoints examining the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months as well as the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months. For inclusion in the investigators’ analyses, individuals were required to have a BMI of 27 kg/m2 or greater and be prescribed weekly semaglutide for 3 months or more. Major exclusion criteria included hoister of bariatric procedures, receipt of other antiobesity medications, and have an active malignant neoplasm.

A total of 408 patients were identified for potential inclusion. After application of exclusion criteria and those who were denied based on insurance or a national shortage of semaglutide, 175 individuals were identified for inclusion in the investigators’ final analyses. This cohort had a mean age of 49.3 (SD, 12.5) years, 75.4% were female, and 88.0% were White. The cohort had a mean BMI of 41.3 (SD, 9.1) kg/m2, 16.0% had type 2 diabetes, and 58.3% had 6-month follow-up data available.

Upon analysis, results indicated the mean weight loss at 3 months was 6.7 (SD, 4.4) kg, which was equivalent to a mean weight loss of 5.9% (SD, 3.7%) (

 <.001). At 6 months, the mean weight loss was 12.3 (SD, 6.6) kg, which was equivalent to a mean weight loss of 10.9% (SD, 5.8%) (

 <.001). Among the 102 patients with at least 6 months of follow-up, 87.3% achieved a weight loss of 5% or more, 54.9% achieved a weight loss of 10% or more, 23.5% achieved a weight loss of 15% or more, and 7.8% achieved a weight loss of 20% or more. Further analysis suggested people with type 2 diabetes had. A lower mean percentage of weight loss at 3 months (3.9% [SD, 3.1%] vs 6.3% [SD, 3.7%]) and at 6 months (7.2% [SD, 6.3%] vs 11.8% [SD, 5.3%]) compared to their counterparts without type 2 diabetes (

“The findings of this cohort study suggest that semaglutide is clinically effective for weight loss at 3 and 6 months for people with overweight or obesity,” investigators added. “Although our study lacked the stringent and closely controlled nature of RCTs, we report similar weight loss results within the same time period as in RCTs. Studies with greater sample sizes and longer periods of follow-up are further needed to support the effectiveness of semaglutide.”

This article originally appeared on Endocrinology Network.

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Real-World Data Backs 2.4 mg Wegovy for Weight Management

 globally is expected to double by 2040, according to the results of a new modeling study.

Funded by JDRF International, results of the study project the number of people with type 1 diabetes worldwide to balloon from 8.4 million, which was the 2021 estimate, up to 13.5-17.4 million by 2040, with the largest relative increases occurring in low- and lower-middle-income countries.

“Given that prevalence of people with T1D is projected to increase in all countries to up to 17.5 million cases in 2040, our results provide a warning for substantial negative implications for societies and healthcare systems,”said study investigator Graham Ogle, MBBS, a pediatric endocrinologist with the University of Sydney, in a statement. “There is an opportunity to save millions of lives in the coming decades by raising the standard of care for T1D and increasing awareness of the signs and symptoms of T1D to enable a 100% rate of diagnosis in all countries. Our model, which will be made available open-source, will make data on the burden of T1D widely accessible and serve as a platform for stakeholders to make improvements in T1D care and outcomes.”

Although type 1 diabetes represents a significant threat to life expectancy, notable gaps in data still exist related to prevalence, incidence, and associated mortality for people with type 1 diabetes. With this in mind, Ogle and a team of colleagues fitted a Markov model with data on type 1 diabetes incidence and associate morality for 201 countries for the year of 2021 to estimate project prevalence in 2040.

Overall, investigators obtained data related to the 1 diabetes incidence form 97 countries and mortality data from 37 countries. For the purpose of analysis, diagnosis rates were estimated using data from an expert survey. Additionally, mortality was modeled using random-first regression of published type 1 diabetes mortality data and life expectancy was calculated using life tables. Investigators pointed out estimates were validated against observed prevalence data for 15 countries.

Investigators found the global prevalence of type 1diabetes in 2021 was approximately 8.4 (95% uncertainty interval [UI], 8.1-8.8) million. Of the 8.4 million with diabetes, 18% were less than 20 years of age, 64% were 20-59 years of age, and 19% were aged 60 years or older. During 2021, investigators estimated there were 500,000 new diagnoses of type 1 diabetes, with a median age at onset of 39 years. Results suggest there were about 500,000 undiagnosed cases in 2021 and, during the same time, investigators estimated about 35,000 undiagnosed patients would die within 12 months of symptom onset.

Investigators highlighted 1.8 million individuals with type 1 diabetes were in low-income and lower-middle-income countries. Comparison of life expectancy revealed the life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. By 2040, the results of the modeling study pointed to an increase in prevalence to 13.5-17.4 million, which represents an increase of 60-107% over the 2021 figures, with the greatest relative increases observed among low- and lower-middle-income countries.

“Our findings indicate that the overall footprint of T1D is much larger than previous estimates have indicated, when missing prevalence due to excess mortality is accounted for,” said study investigator Kim Donaghue, MBBS, PhD, head of Diabetes Complications Assessment Services Child and Adolescent Health at the University of Sydney, in the aforementioned statement. “This is particularly true in low- and middle-income countries – for example in sub-Saharan Africa which accounts for 357,000 cases of T1D or 4% of global prevalence but 23% of the lives lost each year—highlighting the urgent need to increase awareness of the signs and symptoms of T1D in lower-middle-income countries."

1. Gregory GA, Robinson TIG, Linklater SE. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. 

. 2022 Sep 7;S2213-8587(22)00218-2. doi: 10.1016/S2213-8587(22)00218-2.

Modeling indicates a significant increase in patients with type 1 diabetes over the next several years.

Number of People with Type 1 Diabetes Forecasted to Double by 2040

The US Food and Drug Administration has issued an alert to users related to a potential cybersecurity risk for Medtronic MiniMed 600 Series Insulin Pump Systems.

Announced on September 20, the FDA’s alert, which pertains to multiple systems including the MiniMed 630 G and MiniMed 670G, points out the agency had not been made aware of any reports related to this cybersecurity vulnerability. The FDA’s alert also noted 

Medtronic has issued an Urgent Medical Device Correction

 on their own website notifying users as well as providing recommended actions.

“There is a potential issue associated with the communication protocol for the pump system that could allow unauthorized access to the pump system. If unauthorized access occurs, the pump’s communication protocol could be compromised, which may cause the pump to deliver too much or too little insulin,” noted the 

FDA’s September 20 Cybersecurity alert.

On their website, Medtronic provides the Urgent Medical Device Correction, a list of model numbers impacted by the issue, and a multitude of frequently asked questions for device users. Within these resources, Medtronic notes the issue was identified through an internal review and, while the event meets the definition of a recall, users are not required to return their devices.

, which was signed by Chirag Tilara, vice president of Quality at Medtronic Diabetes, and Robert Vigersky, MD, chief medical officer at Medtronic Diabetes, the pair recommended all patients turn off the “Remote Bolus” feature on their pump if it is turned on, which is on by default. The letter also urged users to conduct any connection linking of devices in a nonpublic setting. Additional recommended precautions from Medtronic included keeping pump and connected system components within user control at all times, be attentive to pump notifications, alarms, and alerts, and immediately cancel any boluses you or your care partner did not initiate.

“Medtronic has recently identified a potential issue through internal testing whereby, under specific circumstances, the communication between the components of the pump system could be compromised through unauthorized access,” reads the letter. “For unauthorized access to occur, a nearby person other than you or your care partner would need to gain access to your pump at the same time that the pump is being paired with other system components. This cannot be done over the internet.”

In the aforementioned release, the FDA noted they are working with Medtronic to identify, communicate, and prevent adverse events related to this incident. The FDA urged those with questions to reach out to Medtronic at 1-800-646-4633, option 1.

The risk could allow unauthorized users to change insulin levels.

FDA, Medtronic Alert Users to Cybersecurity Risk with MiniMed 600 Systems

An analysis of online survey data from people with type 2 diabetes is providing new insight into patient preferences related to newer oral therapies in type 2 diabetes.

A custom survey assessing responses to blinded drug profile comparisons comparing empagliflozin 25 mg, oral semaglutide 14 mg, and sitagliptin 100 mg, results of the study provide insight into the most important attributes and most concerning risks pertaining to these newer agents, with results indicating the highest blinded preference score was for the profile matching empagliflozin followed by sitagliptin then oral semaglutide.

“These findings have significant implications as they suggest that patients may be hesitant to initiate guideline-directed medical therapy oral antihyperglycemic therapies with cardiovascular benefit due to side effect concerns,” investigators wrote. “It is possible that these findings reflect a lack of awareness amongst patients of the CV risks associated with T2DM and more focus on side effects and short-term quality of life.”

In recent years, the field of cardiometabolic health has experienced an explosion in knowledge and advancement led primarily by the revelation of the cardiorenal protective benefit provided by some antihyperglycemic agents, such as SGLT2 inhibitors, oral GLP-1 receptor agonists, and DPP-4 inhibitors. However, despite the growing knowledge of these benefits, uptake of these agents has lagged behind, even with inclusion in recent guideline updates.

Patient Survey Details PrefAn analysis of online survey data from people with type 2 diabetes is providing new insight into patient preferences related to newer oral therapies in type 2 diabetes.

Led by Gianluigi Savarese, MD, of the Division of Cardiology at Karolinska Institute, and Abhinav Sharma, MD, of the Division of Cardiology at McGill University, the present study was launched with the intent of developing a more thorough understanding of patient preferences related to oral therapies antihyperglycemic agents. With this in mind, investigators designed the current study as an analysis of data from a custom survey distributed to the dQ&A Diabetes Patient Panel, which is a patient panel of more than 15,000 people with type 1 or type 2 diabetes.

Distributed between August 16-23, 2019, investigators received completed surveys from 553 (67.9%) of the 815 patients contacted and issued surveys. Within the survey, participants were presented with hypothetical, blinded, pairwise, drug profile comparison choices, with benefits and harms derived from phase 3 trials for each agent.

Regarding participant characteristics, 25% had an HBa1c of 6.5-7%, 24% had an HbA1c greater than 8%, 26% had a known history of cardiovascular disease, 55% had cardiovascular disease risk only, and 62% were insulin users. Investigators pointed out all demographic and health outcomes data were self-reported, respondents received $10 for participation in surveys, and the median time to completion was 14.5 minutes.

Upon analysis, investigators found genital infection risk was the most important attribute of an agent’s clinical profile (relative score: 19% [z-test, 

=.077]). The next most important attributes from the patient perspective were fasting requirements (15%), weight reduction (15%), risk of vomiting (14%), cardiovascular benefit (12%), and risk of nausea (11%). Investigators highlighted HbA1c and ability to take other medications were considered the most important factor by 8% and 6% of respondents, respectively. When blinded to drug names and dose, 41% of survey respondents chose a profile similar to empagliflozin, 31% chose a profile similar to sitagliptin, 11% chose a profile similar to oral semaglutide, and 17% elected to choose none of the options.

“These results can facilitate broader conversation between patients and clinicians in determining patient-centric therapies, as advised by the American Diabetes Association and European Society of Cardiology guidelines for type 2 diabetes mellitus treatment and may lead to improved compliance and outcomes,” investigators added in their conclusion.

1. Savarese G, Sharma A, Pang C, Wood R, Soleymanlou N. Patient preferences for newer oral therapies in type 2 diabetes. 

. 2022 Sep 9;S0167-5273(22)01319-5. doi: 10.1016/j.ijcard.2022.09.009

A survey offers new insight into patient preferences related to newer oral therapies in type 2 diabetes.

Patient Preferences for Newer Oral Therapies in Type 2 Diabetes Found in Survey

Results of an open-label trial in people with type 1 diabetes provide data supporting use of open-source automated insulin delivery (AID) systems in children and adults.

Named the Community Derived Automated Insulin Delivery (CREATE) trial, results of the multicenter, randomized trial, which included nearly 100 participants between 7 and 70 years of age from 4 study sites in New Zealand, provide insight into the safety and efficacy of an open-source AID system for use in people with type 1 diabetes, including a 14-percentage point difference in time spent in target glucose range in favor of the trial’s AID and control group.

“In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks,” wrote investigators.

With the rapid rate of advancement in diabetes technology and more and more data detailing the efficacy of open-source AID systems, the CREATE trial was designed and conducted by investigators representing multiple institutions across New Zealand with the intent of adding to this growing knowledge base. With enrollment beginning in September 2020 and lasting through May 2021, the trial’s aim was to compare use of an open-source AID system against a sensor-augmented insulin pump, which served as the control group for the trial. For the purpose of analysis, percentage of time in the target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L between days 155-168, which was the final 2 weeks of the 24-week trial.

The AID system used in the study was a modified version of the AndroidAPS 2.8, with a standard OpenAPS 0.7.0 algorithm paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM. Those randomized to the control arm of the study received either a Dexcom G6 CGM with high and low glucose alerts and their usual insulin pump or a preproduction DANA-i insulin pump to administer bolus insulin doses. Investigators noted the sensor-augmented insulin pump therapy was not designed to predict low-glucose levels or to suspend insulin administration.

A total 48 children and 49 adults underwent randomization, yielding a final cohort of 97 individuals, with 44 randomized to open-source AID and 53 to the control group. Investigators pointed out the unbalanced group size was exacerbated by the number of strata used during randomization. Among the 48 children, 21 were randomized to AID and 27 were randomized to the control group. Overall, this cohort had a median age of 13 (IQR, 9.0-15.0) years, 50% were female, and had a mean time in range of 56.1±11.7% during the run-in period. Among the 49 adults, 23 were randomized to open-source AID and 26 were randomized to the control group. Overall, this cohort had a mean age of 40.0 (29.0-45.0) years, 61% were female, and had a mean time in range of 62.4±14.4% during the run-in period.

At 24 weeks, the mean time in range among the open-source AID group increased from 61.2±12.3% to 71.2±12.1% compared to a decrease from 57.7±14.3% to 54.5±16.0% observed in the control group (adjusted difference, 14 percentage points [95% CI, 9.2-18.8]; 

 <.001), with no treatment effect according to age (

=.56). Further analysis suggested individuals in the open-source AID group spent 3 hours and 21 minutes more in the target range per day than those in the control group of the trial. Investigators highlighted no severe hypoglycemia or diabetic ketoacidosis occurred among either group during the trial. However, investigators noted 2 individuals in the AID group withdrew from the trial due to connectivity issues.

On the Path toward Expanding Treatment Options for Diabetes

,”, Sue Brown, MD, of the Center for Diabetes Technology at the University of Virginia, wrote in support of open-source AID systems based on the results of the current study and previous endeavors. Brown also pointed out the advantages of open-source AID systems against other diabetes technologies currently in use.

“This trial of an open-source configuration showed the superior performance of an AID system in yet another clinical trial, in keeping with remarkably consistent percentages of time in the target glucose range of approximately 70 to 75% across studies of different device types and algorithmic solutions. Investigators in this field strive to improve on these clinical targets by incorporating adjunctive therapies and new insulin formulations along with other innovations that increase ease of use by requiring less user input,” Brown wrote.

Burnside MJ, Lewis DM, Meier RA, et al. Open-source automated insulin delivery in type 1 diabetes. 

 2022; 387:869-881
doi: 10.1056/NEJMoa2203913

Research indicates that using an open-source automated insulin delivery systems can lead to greater glycemic control.

Open-Source Automated Insulin Delivery Systems May Lead to Glycemic Control Improvement in Type 1 Diabetes

A new analysis of data from the SURPASS program suggest use of tirzepatide (Mounjaro) could help people with diabetes reach glycemic targets in a fraction of the time as other medications.

Results of the analysis, which were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting, indicate adults with type 2 diabetes receiving a weekly injection of tirzepatide helped patients reach glycemic targets 4-12 weeks sooner than those receiving semaglutide 1 mg and long-acting insulin degludec.

“Tirzepatide is unique because it mimics two natural insulin-releasing and appetite-suppressing hormones in one injection”, said lead investigator Adie Viljoen, MD, a consultant metabolic physician and chemical pathologist from the East and North Hertfordshire NHS Trust in the United Kingdom, in a statement. “The speed we are seeing in glucose-lowering and weight loss is beyond anything else we have available right now and it may put adults with type 2 diabetes in a better position for preventing long-term complications. But it is important to remember that these medications should be used in addition to diet and exercise.”

With approval of Eli Lilly’s novel dual GIP/GLP-1, which occurred in May 2022, based on the results of the SURPASS program, multiple analyses have been conducted since the initial data release providing further insight into the effects of tirzepatide at different dosages and against different comparators. Available in US pharmacies beginning in June 2022, the agent has been embraced as a potential paradigm-shifting therapy with significant benefits on both diabetes and obesity. In the current study, which was an exploratory preplanned analysis, investigators leveraged data from the SURPASS-2 and -3 trials to assess time to achieve glycemic targets. This was assessed using the Kaplan Meier method and hazard ratios were calculated using Cox proportional hazards model.

In the overall SURPASS-2 trial, use of tirzepatide was compared against use of semaglutide 1.0 mg. Results of the study suggested use of tirzepatide was associated with greater improvements in HbA1cfrom baseline and proportion of people reaching HbA1c goals at 40 weeks. In the SURPASS-3 trial, use of tirzepatide was compared against titrated insulin degludec. Results of the study indicated use of tirzepatide was associated with greater improvements in HbA1c change from baseline and the proportion of patients reaching HbA1c at 52 weeks.

In the present analyses, initial results indicated use of tirzepatide was associated with a significantly faster time to reach HbA1c levels of 7% or lower and 6.5% or lower. The median time to achieve an HbA1c of 7% or below was 8.1 weeks across all tirzepatide doses compared with 12 weeks for semaglutide and 12.1 weeks for titrated insulin degludec. The median time to achieve an HbA1c of 6.5% or below was 12.1 weeks across all tirzepatide doses, 15.7 weeks with semaglutide 1.0 mg, and 24.1 weeks with titrated insulin degludec. In analyses pertaining to weight loss, results indicated tirzepatide was associated with a faster time to achieve 5% change in body weight than semaglutide 1.0, with those receiving tirzepatide achieving this at a median of 12 weeks when using tirzepatide at 10 or 15 mg compared to 24 weeks with semaglutide.

“Even a modest weight loss of 5% of initial body weight is associated with clinically significant improvements in weight-related health issues for many individuals”, Viljoen added in the aforementioned statement. “For people with type 2 diabetes to be able to achieve these improvements in health in around half the time is pretty incredible.”

This study, “Patients with type 2 diabetes reach glycaemic targets faster with tirzepatide compared to semaglutide and titrated insulin degludec,” was presented at EASD.

New research offers evidence that tirzepatide could help patients achieve glycemic goals.