<b>Objective</b>
<p>Despite
advances in exogenous insulin therapy, many patients with type 1 diabetes do
not achieve acceptable glycemic control and remain at risk for ketosis and
insulin-induced hypoglycemia. We conducted a randomized controlled trial to
determine whether TTP399, a novel hepatoselective glucokinase activator,
improved glycemic control in people with type 1 diabetes without increasing
hypoglycemia or ketosis. </p>
<p><b>Research design and methods</b></p>
<p>SimpliciT1 was a Phase 1b/2
adaptive study. Phase 2
activities were conducted in 2 parts. Part 1 randomized 20 participants using
continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion
(CSII). Part 2 randomized 85 participants on multiple daily injections of
insulin or CSII. In both Part 1 and 2, participants were randomized to TTP399
800 mg or matched placebo (fully blinded) and treated for 12-weeks. The primary
endpoint was the change in HbA1c from baseline to week 12.</p>
<p><b>Results</b></p>
<p>The
difference in the change in HbA1c from baseline to week 12 between TTP399 and
placebo was -0.7% (95% CI -1.3, -0.07) in Part 1 and -0.21 (95% CI -0.39,
-0.04) in Part 2. Despite a greater decrease in HbA1c with TTP399, the
frequency of severe or symptomatic hypoglycemia decreased by 40% relative to
placebo in Part 2. In both Part 1 and Part 2, plasma beta-hydroxybutrate and
urinary ketones were lower during treatment with TTP399 than placebo. </p>
<p><b>Conclusions</b></p>
<p>TTP399
lowers HbA1c and reduces hypoglycemia without increasing the risk of ketosis
and should be further evaluated as an adjunctive therapy for the treatment of
type 1 diabetes.</p>
Short-acting glucagon-like peptide-1 receptor agonists as add-on to insulin therapy in type 1 diabetes: A review
