Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)

• ESG with OverStitch (Device): Endoscopic Sleeve Gastroplasty (ESG) with OverStitch Endoscopic Suturing System.

Primary outcomes

• Serious Adverse Events [Through study completion, 12 months post procedure]: Serious Adverse Events related to the study procedure and/or study device defined as Grade III or greater according to Clavien-Dindo Classification
• Average Change in HbA1c [12 months post procedure]: Mean change in HbA1c from baseline to 1-year. If rescue treatment is initiated, the last HbA1c value before initiation of rescue treatment is used for assessment of the primary effectiveness endpoint.

Secondary outcomes

• Proportion of Subjects Achieving HbA1c < 7% [12 months post procedure]: Proportion of subjects achieving HbA1c < 7% without initiating rescue treatment at 1-year

Other outcomes

• Weight Loss [1, 3, 6, 9, and 12 months post procedure]: Total Body Weight Loss (TBWL) % and Excess Weight Loss (EWL) % at each visit
• Proportion of Subjects with a Total Body Weight Loss ≥ 10% [1, 3, 6, 9, and 12 months post procedure]: Proportion of subjects with a TBWL ≥ 10% at each visit
• Proportion of Subjects Achieving HbA1c < 6.5% [12 months post procedure]: Proportion of subjects achieving HbA1c < 6.5% without initiating rescue treatment at 1-year
• Proportion of Subjects Achieving TBWL ≥ 10% AND HbA1c < 6.5% [12 months post procedure]: Proportion of subjects with a TBWL ≥ 10% AND a HbA1c < 6.5% without initiating rescue treatment at 1-year
• Proportion of Subjects Initiating Rescue Treatment [Through study completion, 12 months post procedure]: Proportion of subjects initiating rescue treatment at any time during the study follow-up period
• Proportion of Subjects Meeting Rescue Criteria [Through study completion, 12 months post procedure]: Proportion of subjects meeting rescue criteria at any time during the study follow-up period
• Proportion of Subjects with Improvement in Comorbidities [12 months post procedure]: Proportion of subjects with improvement in each specific obesity-related comorbidity, as applicable, from baseline to 1-year: Hypertension, Dyslipidemia, Obstructive sleep apnea, Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
• Change in Vitals [6 and 12 months post procedure]: Change in vitals from baseline to 6-months and from baseline to 1-year: Systolic blood pressure, Diastolic blood pressure
• Change in Blood Laboratory Tests [6 and 12 months post procedure]: Change in blood laboratory tests from baseline to 6-months and from baseline to 1-year: fasting plasma glucose, estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST), alanine aminotransferase (ALT,) low-density lipoprotein cholesterol (LDL-C), Triglycerides
• Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [6 and 12 months post procedure]: Change in HOMA-IR from baseline to 6-months and from baseline to 1-year
• Change in Fibrosis-4 (FIB-4) [6 and 12 months post procedure]: Change in FIB-4 from baseline to 6-months and from baseline to 1-year
• Change in Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score [6 and 12 months post procedure]: Change in NAFLD Fibrosis Score (NFS) from baseline to 6-months and from baseline to 1-year
• Change in Diabetes Treatment Satisfaction [12 months post procedure]: Change in diabetes treatment satisfaction, as assessed by Diabetes Treatment Satisfaction Questionnaire - status (DTSQs), from baseline to 1-year and Diabetes Treatment Satisfaction Questionnaire - change (DTSQc) at 1-year; Positive score indicates an improvement in satisfaction, or a reduction in the frequency of hyper/hypoglycemia. Negative score indicates a deterioration in satisfaction, or an increase in the frequency of hyper/hypoglycemia. Zero indicates no change in satisfaction or symptoms.
• Change in Diabetes Self-Care Activity [6 and 12 months post procedure]: Change in diabetes self-care activity, as assessed by Summary of Diabetes Self-Care Activity (SDSCA), from baseline to 6-months and from baseline to 1-year; Higher scores indicate better compliance with diabetic self-care recommendations. Lower scores point to areas where the patient may be struggling or may need additional education and support.
• Change in Quality of Life [12 months post procedure]: Change in quality of life, as assessed by 36-Item Short Form Health Survey (SF-36) domain scores and Physical and Mental Component Summaries (PCS and MCS), from baseline to 1-year; Higher scores indicate a better, higher quality of life and fewer health-related limitations.
• Adverse Events [Through study completion, 12 months post procedure]: Adverse events associated with study procedure and/or study device

Sex: All, ages: 22 Years to any

Inclusion Criteria:

* Willing and able to provide written informed consent to participate in the study
* Age ≥ 22 years
* BMI 30 - 50 kg/m2
* HbA1c 7.5 - 10.5%
* Type 2 Diabetes treated with incretin-based medication (aka GLP-1RA agonist or GLP-1RA/GIP dual agonist) at a stable, maximal tolerated dose for a minimum of 6 months +/- any other oral glucose lowering medications AND intention to initiate insulin therapy for glycemic management
* Stable weight (< 5% TBW) within the 3 months prior to screening
* Meets the indications for ESG procedure with OverStitch™ or OverStitch NXT™ Endoscopic Suturing System, excluding the following but not limited to the following: large hiatal hernia, potential bleeding gastric lesions (e.g. ulcers; erosive gastritis; varices; or vascular malformation), coagulopathy and antiplatelet/anticoagulant therapy that cannot be corrected
* Declines or is ineligible for metabolic bariatric surgery
* Agrees to abstain from taking any weight loss treatments or supplements that are not part of the lifestyle modification program for a year following the ESG procedure
* Willing and able to comply with the study procedure with standard of care lifestyle modification program and visit schedule.

Exclusion Criteria:

* Diabetes management with insulin. Prior use of insulin for gestational diabetes or short-term use (up to 1 month) in conjunction with an acute condition is acceptable.
* Noncompliance with medication regime for diabetic management
* More than one episode of clinically significant reactive or severe hypoglycemia within the prior 1 year. Reactive hypoglycemia is defined as postprandial hypoglycemia meeting Whipple's Triad; severe hypoglycemia is defined as any hypoglycemic episode requiring assistance from another person to administer carbohydrates, glucagon, or other corrective/resuscitative action
* History of ketoacidosis or hyperosmolar nonketotic coma within the past 1 year
* Has a contraindication for ESG procedure with OverStitch™ or OverStitch NXT™ Endoscopic Suturing System, including but not limited to the following: large hiatal hernia, potential bleeding gastric lesions (e.g. ulcers; erosive gastritis, varices, or vascular malformation), coagulopathy and antiplatelet/anticoagulant therapy that cannot be correct
* Prior gastric surgery, including but not limited to LSG or RYGP
* Any known conditions that impact weight loss or glycemic management
* Chronic systemic steroids or immunosuppressants taken at the time of enrollment or likely required during the study follow-up
* CKD stage 3+, defined as eGFR < 60 mL/min
* Persistent anemia, defined as hemoglobin < 10 g/dL
* Excessive alcohol consumption, defined as meeting or exceeding sex-based heavy drinking limits
* Use within the last three months prior to screening of over the counter or prescribed weight loss supplements / medications, or intent to use any weight loss medications or supplements during the study duration.
* The investigator's medical judgment that the subject is not a candidate for the ESG procedure due to findings, including but not limited to psychological and nutritional evaluation results obtained in the prior 12 months.
* Current pregnancy confirmed by site standard of care or planned pregnancy or breastfeeding for a year following the ESG procedure.
* Vulnerable subject.
* Current or planned participation in another clinical study.

• Ildiko Lingvay, MD, Principal investigator, UT Southwestern
• Shailendra Singh, MD, Principal investigator, West Virginia University