Since the 1970s, extensive experimental and clinical research has demonstrated that relevant reductions of creatine phosphate (CrP) or phosphocreatine availability occur in a wide spectrum of pathophysiological situations. A decrease in intracellular concentrations of creatine (Cr) and CrP results in a hypodynamic state of cardiac and skeletal muscle pathology. Many experimental and clinical studies have evaluated the possibility to improve cardiac and skeletal muscle performance by exogenous administration of CrP. Furthermore, many experimental studies have shown that CrP may play two important roles in the regulation of muscle energetics and work. First, CrP maintains local adenosine triphosphate pools and stabilizes cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic hearts, protects the sarcolemma of cardiac cells against ischemic damage, decreases the frequency of arrhythmias, and increases post-ischemic recovery of contractile function. Recent research on CrP has demonstrated positive therapeutic results in various clinical applications. These benefits have been applied in several pathological conditions, such as heart failure, acute myocardial ischemia, chronic ischemic heart disease, cardiac surgery, skeletal muscle hypotonotrophy, and cerebral ischemia. This review describes the CrP shuttle, pathophysiological basis of the supplementation of CrP, and its therapeutic effects in multiple clinical conditions. The major aim is to summarize results of the intense research carried out over 40 years to provide evidence to support the adjunctive use of CrP in many pathological conditions that may target cellular energy impairment; thus, increasing energy metabolism.

Introduction: Combining antihyperglycemic agents with complementary mechanisms of action is a cornerstone of type 2 diabetes mellitus (T2DM) management. Although several fixed-dose combinations (FDCs) are available, representing standard types of combination therapy in T2DM, use of these products has been limited. Methods: To address the likely concerns of prescribers and patients regarding the use of FDCs in the treatment of T2DM, literature searches were performed to ascertain the bioavailability, efficacy, tolerability, and cost-effectiveness of the currently approved FDCs compared with their individual component drugs given as separate pills in combination. Additionally, data were collected on rates of adherence, clinical outcomes, and overall treatment costs with FDCs versus dual therapy with the same constituent drugs. Results: Bioavailability is equivalent for FDCs and dual therapy used in T2DM. Efficacy and tolerability also appear to be at least as good with FDCs as with dual therapy. Retrospective analyses have suggested that FDCs can enhance adherence to therapy, presumably as a result of the reduction in pill burden, and improved adherence may result in improved glycemic control and reduced disease management costs. In addition, because currently available FDCs come in two or more dose-strength formulations, they also afford some measure of dosing flexibility. Conclusions: The available evidence supports the wider use of FDCs in the treatment of patients with T2DM.

Since the 1970s, extensive experimental and clinical research has demonstrated that relevant reductions of creatine phosphate (CrP) or phosphocreatine availability occur in a wide spectrum of pathophysiological situations. A decrease in intracellular concentrations of creatine (Cr) and CrP results in a hypodynamic state of cardiac and skeletal muscle and cardiac and muscle pathology. Many experimental and clinical studies have evaluated the possibility to improve cardiac and skeletal muscle performance by exogenous administration of CrP. Furthermore, many experimental studies have shown that CrP may play two important roles in the regulation of muscle energetics and work. First, CrP maintains local adenosine triphosphate (ATP) pools and stabilizes cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic hearts, protects the cardiac cells sarcolemma against ischemic damage, decreases the frequency of arrhythmias, and increases the post-ischemic recovery of contractile function. Recent research on CrP has demonstrated positive therapeutic results in various clinical applications. These benefits have been applied in several pathological conditions, such as heart failure, acute myocardial ischemia, chronic ischemic heart disease, cardiac surgery, skeletal muscle hypotonotrophy, and cerebral ischemia. This review describes the CrP shuttle, the pathophysiological basis of the supplementation of CrP, and its therapeutic effects in multiple clinical conditions. The major aim is to summarize the results of the intense research carried out over 40 years in order to provide evidence that clearly support the adjunctive use of CrP in many pathological conditions that may take advantage from targeting cellular energy impairment; thus, increasing energy metabolism.