This will be a placebo-controlled, randomized, double blind, crossover study with a 4 week wash out period.

Collect pilot data on the safety, tolerability, and feasibility of empagliflozin therapy in overweight/obese patients with CFRD to support a future larger randomized controlled trial.

The overall goal of this proposal is to collect pilot data for safety and feasibility metrics to support a future larger randomized controlled trial. In this study, we will examine the safety and tolerability of Sodium glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin as an add-on therapy to insulin for overweight/obese adult patients with CFRD. We hypothesize that empagliflozin will be safe, well tolerated and will improve glycemic control in overweight/obese adult patients with CFRD.

Specific Aim 1: Collect pilot data on the safety, tolerability, and feasibility of empagliflozin therapy in overweight/obese patients with CFRD to support a future larger randomized controlled trial.

Hypothesis 1: Empagliflozin will be safe and well tolerated, with no evidence for electrolyte abnormalities, metabolic acidosis, ketosis or increased risk of severe hypoglycemia in overweight/obese adults people with CFRD.

Specific Aim 2: Collect preliminary data to evaluate the effect of empagliflozin on glycemic outcomes.

Hypothesis 2: Treatment with empagliflozin will improve glycemic control as indicated by glucose levels as measured by oral glucose tolerance test (OGTT), and on glycemic outcomes as measured by continuous glucose monitoring (CGM).

Inclusion Criteria:

• Adult subjects 18 years or older with CFRD and on insulin treatment
• BMI >25 kg/m2
• A participant who is capable of becoming pregnant must agree to take precautions that are effective in preventing pregnancy throughout this study. These methods could include one of the following 1. Complete abstinence from sexual intercourse; 2. Tubal ligation; 3. Use combination of two forms of contraception during the study including, oral, injectable, or implanted hormonal contraceptives, intrauterine device or barrier method.

Exclusion Criteria:

• acute pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to baseline study procedures
• less than 12 weeks since start of a new CFTR corrector/modulator therapy
• type 1 diabetes
• Positive GAD 65 antibody or low fasting C-peptide (below the normal reference range of the lab)
• A history of diabetic ketoacidosis
• history of recurrent genital or urinary tract infections
• pregnancy or lactation
• prior solid organ transplant
• Chronic liver disease (based on problem list in medical records or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times elevated above the upper limit of normal.
• chronic kidney disease (eGFR < 60mL/min/1.73 m2)
• Hypersensitivity to empagliflozin or any excipients of Jardiance
• History of eating disorder
• Non-English speakers and those unable to read in English • Diminished capacity to consent (study staff will utilize the MacCAT-CR for assessment)

double-blind