CGM-Guided Acarbose for Painful Diabetic Neuropathy

Shifa International Hospital170 enrolled

Overview

This Phase II pragmatic hybrid effectiveness-implementation trial tests whether acarbose, titrated using continuous glucose monitoring (CGM) to blunt post-prandial excursions, reduces 4-week pain area-under-the-curve (AUC) versus placebo in adults with painful diabetic peripheral neuropathy (DPN) and high glycemic variability. Secondary objectives assess CGM variability metrics, microvascular reactivity, inflammatory markers, safety, and feasibility of a pharmacist-led titration workflow using loaner CGMs across multi-region community clinics.

Adults with T2D, painful DPN, and high CGM variability (e.g., MAGE \>50 mg/dL on run-in) are randomized 1:1 to acarbose vs matching placebo for 4 weeks, on stable background analgesics. A standardized pharmacist-led algorithm escalates acarbose to target post-prandial spikes, guided by blinded CGM trend review. The primary endpoint is 4-week daily pain AUC captured via ePRO. Key secondary endpoints include changes in MAGE and time-in-range (TIR), skin microvascular reactivity (laser speckle), serum IL-6, patient global impression of change, rescue-analgesic use, and adverse events. Implementation outcomes (acceptability, feasibility, adoption, cost) are collected to inform scale-up in HIC and LMIC community settings.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

170

Conditions

Diabetes Diabetes Complications

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion: * Age 18-75 years. * Type 2 diabetes ≥1 year; HbA1c 7.0-10.0% within 8 weeks of randomization. * Painful DPN meeting clinical criteria; average daily pain NRS ≥4 during run-in. * High CGM variability on 7-10 day run-in (e.g., MAGE \>50 mg/dL). * Stable analgesic regimen ≥4 weeks pre-baseline. * Able to use CGM and ePRO; provides informed consent. Exclusion: * Type 1 diabetes; non-diabetic neuropathies. * Contraindications to acarbose (e.g., chronic intestinal malabsorption, inflammatory bowel disease). * eGFR \<45 mL/min/1.73 m²; significant hepatic disease (ALT/AST \>3× ULN). * Use of α-glucosidase inhibitors within 3 months. * Recent change (\<3 months) in GLP-1/GIP agonists, SGLT2i, or basal/bolus insulin strategy. * Pregnancy/lactation; other conditions compromising safety/assessments.

Outcomes

Primary Outcomes

Daily pain AUC

Daily pain AUC (ePRO; 0-10 NRS). Method: trapezoidal AUC of daily NRS scores; higher AUC = worse pain. Daily pain area under the curve derived from the Numeric Rating Scale for Pain (NRS). The NRS ranges from 0 to 10, where 0 = no pain and 10 = worst imaginable pain. Higher scores indicate worse pain. AUC is calculated using the trapezoidal method from daily NRS scores over the assessment period. Higher AUC values indicate greater overall pain burden.

Time frame: baseline→Week 4

CGM MAGE (mg/dL)

Time frame: baseline→Week 4

Secondary Outcomes

CGM Time-in-Range (70-180 mg/dL, %)

Time frame: baseline→Week 4

Skin microvascular reactivity

Skin microvascular reactivity by laser speckle contrast imaging

Time frame: baseline→Week 4

Serum IL-6

Serum IL-6 (pg/mL)

Time frame: baseline→Week 4

Patient Global Impression of Change (PGIC)

Patient Global Impression of Change (PGIC). Patient Global Impression of Change (PGIC) assessed on a 7 point Likert scale ranging from 1 = very much improved to 7 = very much worse. Lower scores indicate improvement; higher scores indicate worsening.

Time frame: Week 4

CGM-Guided Acarbose for Painful Diabetic Neuropathy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes