How do you define &quot;minor&quot;?  These insulins have dramatically different serum half lives (for example there are fast acting ones for postprandial administration, others that are optimized for pumps, etc) and so there is a clear pharmacological difference.  Moreover, discovering these variants is nontrivial, as each insulin must be checked against igf-1 receptor cross reactivity, lest it become teratogenic.  Making matters worse, the exact binding of insulin and igf-1 to their receptors is not known making this endeavor especially difficult to predict.<p>What is not clear is whether these modifications are an over optimization over &quot;the original&quot;.  For each patient the cost&#x2F;benefit calculation will be different and based on many variables.